theory 50% lect+tut+hot topics Flashcards

Question

what is the RQ for protein

Answer 1

1. HR 2. double- labelled water 3. measures of physical activity 4. questionnaires 5. movement monitors

Answer 2

ratio of VCO2/VO2, it is guide to the mixture of nutrients being oxidised

Answer 3

HR is proportional to O2 consumption, O2 consumption is an indirect way of measure energy expenditure

Answer 4

MET (Metabolic Equivalent Task) Factor estimates intensity of a single activity as a multiple of BMR • PAL (Physical AcUvity Level) Factor estimates the total daily physical acUvity as a mulUple of BMR

Answer 5

1. appetite 2. foraging 3. ingestive behavior and 4. energy saving

Answer 6

1. satiation | 2. energy expenditure

Answer 7

‘Humans are flexible converters of food energy, able to respond with altered metabolic efficiencies to different diets, environmental conditions, specific tasks and health states’

Answer 8

``` energy reserve (body weight) increase or decrease depend on absorption and energy output. absorption of proteins, gats and carbohydrates, these energy used to do physical activity, energy for absorption and nutrient storage and BMR ```

Answer 9

these depends on factors that influence amount of energy intake and expenditure. which include endogenous and exogenous factors

Answer 10

1. endogenous - biological and psychological (cognitive) 2. exogenous

Answer 11

-biological -psychological (cognitive) biological include: 1. appetite/hunger (the desire to eat) 2. satiation (the signal to bring eating to an end) 3. satiety (the suppression of appetite/ hunger) 4. basal metabolic rate ( body composition, age etc) 5. thermic effect of food (energy expended to digest and absorb nutrients) 6. phyical activity

Answer 12

1. physical (e.g. music pace) 2. social 3. economic

Answer 13

1. genes (determine gender, which in turn determine the body composition ) 2. height, weight 3. gender 4. metabolic changes (lactation, pregnancy, growing, disease state) 5. age 6. percent fat vs muscle 7. surface area 8. climate 9. hormone 10. drugs

Answer 14

women=146 kj/m2/hour | men=159 kj/m2/hour

Answer 15

kids have high BMR per kg body weight, because they r growing and developmenting - the metabolic rate about orgaans stay the same, the children have high metabolic active organs because they have more fat-free mass contribute to organs . - the BMR per kg of organ per day stay the same, they chew a lot of energy, as we grow, the organs make less in our body mass.

Answer 16

liver, brain, heart and kidneys have high metabolic rate (kJ/kg/d). however the daily energy expenditure is calculated by metabolic rate x weight. the skeletal, liver, brain and residual mass have high energy usage per day (kJ/d)

Answer 17

* Insulate by becoming obese * Boost BMR to generate more heat * Cut conductance through vasoconstriction • Create a portable microenvironment

Answer 18

in disert, the aborigines have no difference in BMR overnight, become they dont shiver, their body vasoconstrict, therefore they spend less energy compare to white. the white man have dramatic changes over night for BMR because they shiver

Answer 19

• Energy balance = balance of energy from protein, fat, carbohydrate - the energy expenditure is continuum, some energy is stored to maintain this

Answer 20

nutrient intake - nutrient utilisation = change in body nutrient reserves this follow the law of conservation of mass 3 possible outcomes: zero balance, positive balance, negative balance.

Answer 21

• Nitrogen balance = protein balance

Answer 22

``` 1. low-carb diets: energy balance with - negative car balance - positive fat balance 2. diet negative energy balance 3. pregnant positive balance most nutrients 4. growth in childhood positive energy balance positive nitrogen balance 5. illness and severe trauma negative energy balance negative nitrogen balance ```

Answer 23

Most metabolic substrates are being continually utilised and replaced e.g. protein in diet -> amino acid metabolism in tissue-> urea synthesis for excretion the amino acid metabolism in tissue and body protein are continuous turnover

Answer 24

the glucose level is dynamic steady state. the insulin is secreted to maintain blood glucose level after a meal/

Answer 25

fed state: beta cell increase amylin, and insulin, alpha cell decrease glucagon. glucagon and insulin send signal to liver to decrease glucose production, therfore decrease glucose from the liver to Blood vessel fastinf state: glucagon secreted, decrease insulin, gluconeogenesis-> increase glucose production, glycogenolysis -> change to glucose this will increase glucose production, therefore maintains glucose in blood stream

Answer 26

FLUX = rate of flow of a nutrient through a metabolic pathway eg the flux of glucose from blood to tissues = 2mg/kg body weight/min • blood glucose stays steady because liver matches glucose production • Net flux = 0 • Cellular, tissue or whole body level • Dependent on the metabolic pool source of the nutrient

Answer 27

3. 1.Precursor pool • Provides substrate from which the nutrient/metabolite is synthesised 2. Functional pool • Nutrient/metabolite has direct role in one or more bodily functions 3. Storage pool • Buffer of nutrient/metabolite that can be made available for the functional pool

Answer 28

• Provides substrate from which the nutrient/metabolite is synthesised

Answer 29

• Nutrient/metabolite has direct role in one or more bodily functions

Answer 30

• Buffer of nutrient/metabolite that can be made available for the functional pool

Answer 31

- available energy can be synthesized in the liver and muscle to form glucose/glycogen - adipose makes triglyceride, which can be used as energy source - muscle have mobilisable protein which can be used for energy

Answer 32

Regulatory mechanisms in the body manage to store excess food energy and release it as we need it. • Nervous system - Central nervous system • Endocrine systems - Hormonal control

Answer 33

alpha cells secrete glucagon, beta cellls secrete insulin and amylin

Answer 34

• Peptide hormone • Synthesised as preproinsulin • Secreted as two peptide chains (A & B) linked by disuphide bond • Secretion regulated by plasma glucose concentration, amino acids • Insulin stored in secretory granules and released by exocytosis

Answer 35

1. insulin is made firstly with preproinsulin which is A chain and B chain 2. preproinsulin convert to proinsulin. the A chain connected to B chain by a connecting peptides which is called C chain 3. then the C chain is cleaved off in the secretory granules, insulin is secreted in the active form

Answer 36

• Single polypeptide chain synthesised as proglucagon, then in the pancreas, glucagon is secreted.

Answer 37

• Major action is to elevate blood glucose levels

Answer 38

* Stimulated by low glucose and high amino acids | * Suppressed by rise in blood glucose concentration

Answer 39

* Main target tissue liver – 5-10% removed in first passage | * Binds glucagon receptor, works via activation of adenylyl cyclase and cAMP second messenger

Answer 40

1. the plasma glucose conc. is changing with the meal 2. insulin is secreted to reduce the flutuation of the blood glucose 3. glucagon is secreted in the fasting dips to make sure blood glucose level dont drop too far

Answer 41

``` • Short term effects • Mediated through changes in protein synthesis (hours) • Fat mobilisation (increases HSL) • GNG(gluconeogenesisi) • Reduced muscle glucose uptake • Increase muscle protein breakdown ```

Answer 42

• Sets the tone of response to other hormones • Permissive effects

Answer 43

secrete from fat tissue - reflect how much fat we have in the body - directly tell the brain to stop eating - increase energy expenditure in mice,

Answer 44

› The proportion in which chemical components contribute to body mass › Determined by the interaction between genetics and nutrition

Answer 45

› Nearly every aspect of clinical nutrition and exercise science uses body composition research › Body composition changes with growth, development, pregnancy, lactation, ageing, exercise and disease › Abnormal body composition is associated with disorders and disease › Body composition is highly variable between individuals

Answer 46

1. atomic 2. molecular 3. cellular 4. tissue/organ 5. whole body

Answer 47

oxygen, carbon, hydrogen, nitrogen, calcium, phosphorus

Answer 48

``` Over 100 000 chemical compounds › Water – extra- / intracellular ~60% › Lipids - ~17% › Protein - ~17% › Carbohydrates – mainly glycogen › Minerals – bone & soft tissue ```

Answer 49

``` Cellular › Body cell mass – 10^18 cells › Extracellular fluids › Extracellular solids Tissue ->Body weight = adipose Ossue + skeletal muscle + bone + organs + ... ```

Answer 50

10 dimensions generally considered 1. Stature – indicates general body size and skeletal length 2. Segment lengths of limbs 3. Body breadth – measures of body shape, skeletal mass and frame size 4. Circumferences eg waist circumference indicator of adiposity 5. Skinfold thickness – for esOmaOng fatness and distribuOon of subcutaneous fat 6. Body surface area – used to esOmate basal metabolic rate 7. Body volume – indicates body size and used to determine body density 8. Body mass 9. Body mass index (BMI) body mass (kg)/height m2 10. Body density used to indirectly determine fat free mass

Answer 51

1. direct 2. indirect 3. double direct

Answer 52

- Carcass analysis | - in vivo neutron activation analysis

Answer 53

- densitometry - deuterium oxide dilution - radioactive potassium ^40 counting - more compartment models - dual energy X ray - absorptiometry - CT/MRI scans

Answer 54

- weight/height indices - skinfolds/ultrasound - circumference/diameter - impedance - infrared interactance - creatine excretion

Answer 55

hydrodensitometry

Answer 56

it is an indirect measurement od body composition › Based on Archimedes principle: - volume of object = volume water displaced - Underwater weighing density of fat=0.9 g/cm^3 density of fat-free =1.100g/cm^3

Answer 57

slide 12 L4

Answer 58

it is an indirect measurement of body composition, belong to densitometry. using body pod. Bod Pod Two chambers (test, reference) separated by diaphragm Pressure of air increased by adding a known volume of air into chamber. Based on Boyle’s law to calculate volume: P1/P2 = (V2/V1)

Answer 59

slide 15 and 16 L4

Answer 60

it is an indirect method for measuring body composition . Also used to determine fat free mass. Potassium is present within cells but not associated with stored fat. 40K natural isotope of potassium (0.012% of all K), emits γ rays Measurement of 40K radiation from the body for TBK K in lean mass is variable and dependent on sex, age and BMI. Assume men: 60 mmol / kg FFM women: 66 mmol / kg FFM

Answer 61

it is an indirect method for measuring body composition .

Answer 62

DEXA Dual-energy x-ray absorptiometry Body is scanned with x-rays of 2 distinct energy levels The amount of energy not absorbed by tissues is detected by photocells Tissue absorption of radiation is determined by its chemical composition – allowing us to distinguish between bone, lean tissue and adipose.

Answer 63

``` Common measures › BMI = Body mass index mass (kg) height (m) › Waist, hip circumference › Skin fold thickness ```

Answer 64

= weight(kg)/height(m^2) Healthy weight range is usually defined in terms of body mass index (BMI) normal between 18.5 -24.9

Answer 65

it is a surrogate marker of visceral fat. men, greater than 102 cm=increased risk women, greater than 88 cm=increased risk

Answer 66

high BMI have very high motality ratio due to cardiovascular and gallbladder disease and diabetes mellitus low BMI have moderate motality ratio due to digestive and pulmonary disease

Answer 67

``` › Ethnicity › Gender › Age › Body build › Epigenetics ```

Answer 68

Epigenetic gene regulation is a binary system: “On” or “Off” | Epigenetic states are probabilistic – every locus has some probability of being silent

Answer 69

nucelosome packaging determines chromatin structure and transcription state

Answer 70

Epigenetic modifications allow cells with precisely the same genomes to adopt a multitude of phenotypes based on the activity of some loci and the silencing of others -Cell differentiation is epigenetic gene regulation par excellence ~25,000 genes in human genome – each cell type uses only a proportion, and the remainder are silent

Answer 71

Epigenetics is interposed between genes and environment -Epigenetic modifications mediate genome function and are responsive to environmental cues: cellular, organisismal, external

Answer 72

The probability of epigenetic errors may be influenced by the environment and the most vulnerable time is during our development when cellular epigenotype is set

Answer 73

The intrauterine environment is inescapable: nutritional stress during gestation can have life-long health consequences - a baby with low birth weight is more likelt to develop hypentension and CVD in the late middle age

Answer 74

We now know that undernutrition, overnutrition, or an altered supply of key nutrients during gestation can all induce metabolic syndrome and other symptoms in offspring: this effect is called FETAL PROGRAMMING, or developmental origins of health and disease - adverse fetal environment followed by plentiful food in adulthood maybe a recipe for adult chronic disease.

Answer 75

an increase number of women are going into pregnancy overweight or obese an increase number of overweight and obese men are fathering children

Answer 76

- Overnutrition as well as obesity per se - Periconceptional period may be as important as gestation - Metabolism not the only trait affected periconceptional period: the time that the oocyte is maturing 1 or 2 month before ovulation through to conception implaintatio

Answer 77

... Epigenetic changes to gene expression

Answer 78

A sophisticated program that usually goes according to plan How can two specialised cells (sperm and ova), with their own specific phenotypes and epigenotypes, come together to create a totipotent zygote? What mechanisms are in place to avoid epigenetic errors being propagated to offspring?

Answer 79

- once the fertilization happens. the first embryooic epigenetic resetting take place, the male genome rapidly demthylated and female demethylated at a slower rate. This allows 1. Restoration of pluripotency 2. Embryonic gene expression 3. Early lineage development 4. Parental imprinting marks spared - at theblastocyst stage, a second round of epigenetic resetting take place. this allow: “Clean the slate” for the next generation – remove epimutations, set germ-cell specific marks Parental imprints erased and reset

Answer 80

aberrant epigenetic silencing of a normally active gene | or, occasionally, aberrant activation of a normally silent gene

Answer 81

This epimutation occurs on a uniform genetic background

Answer 82

yes. Epigenetic dysregulation is a hallmark of cancer - cancer cell methylate and silence a lot of genes that cancer cell dont want to be active e.g. mutation repair gene, apoptosis gene and any gene cause cancer cell to shut off - retrtransposon often activated to cause more mutation in the cancer cells > they are jumping gene cause more mutation in the genome

Answer 83

familial cancer: germline mutation that passes from parent to children, they have predisposition for cancer around age 50 years old. - some member in family look like they have the sydrome but have no mutation in DNA. - 1 pair of mismatching gene called MLH1 has silenced in everycells in his body by methylation .

Answer 84

Non-mendelian inheritance of the MLH1 germline epimutation in humans - epigenetic resetting in the germline is there to wipe off epigenetic mistake, it's clearly it doesnt work all the time.

Answer 85

Transgenerational epigenetic inheritance The transmission of an allele’s epigenotype through MEIOSIS – so that the epigenotype of the offspring resembles that of the parent. Importantly, this does not generally occur in lockstep with the inherited genotype, so the pattern of inheritance is NON-MENDELIAN

Answer 86

* Paramutation | * Transposon silencing

Answer 87

Epigenetic states are generally reset between generations Some sequences escape resetting e.g. centromeres, some retrotransposons ... any genes?

Answer 88

* Inheritance of Fab7 activity in Drosophila Melanogaster * Inheritance of gene expression changes in mice after embryo manipulation (also the first instance of inherited environmental effects – more on this in a minute!) * Inheritance of transgene silencing in mice – several reports

Answer 89

a model of epigenetic variation, and inheritance - an insertion of transposon upstream of agouti coat colour gene. - Avy is epigenetically regulated - Activity/silence correlates with DNA methylation at the IAP promoter region

Answer 90

Avy epigenotype is partially heritable – but only when maternally transmitted

Answer 91

Avy mice are also a model of epigenetic response to early environment - Gestational exposure to various nutritional stressors alters the spectrum of offspring coat colour phenotypes - he epigenetic effect of methyl donor supplementation on Avy is heritable: you are what your grandmother ate! - The epigenetic effects of maternal undernutrition may be heritable also

Answer 92

Paternal effects: intergenerational transmission of father’s condition - if thefather have diabetes, the children is smaller. - the birth weight predict T2D in later life

Answer 93

Yellow Avy mice are obese and insulin resistant but not frankly diabetic, mirroring the phenotype of most obese individuals (particularly men) of reproductive age -Obese Avy parents induce metabolic defects in their wild-type offspring

Answer 94

We have recently used Avy to model paternal obesity and find that both sons and grandsons of obese males are similarly predisposed to metabolic dysfunction. We find epigenetic changes in their SPERM!

Answer 95

* Both maternal AND paternal obesity programs an increased disease risk in offspring, independently of the inherited DNA sequence, that can be passed on to subsequent generations. * Programming is associated with widespread gene expression and epigenetic changes – these are likely maladaptive changes for the individual, and may be linked to deleterious phenotypes beyond metabolism.

Answer 96

* Having an obese parent – or grandparent – predisposes to metabolic disease. * Predisposed individuals can propagate the latent metabolic phenotype even if they themselves do not exhibit metabolic disease. * Maintaining a healthy diet prevents the onset of overt disease in programmed individuals; exposure to a Western diet exacerbates the deleterious health effects.

Answer 97

Often an ill-defined term – usually assumed someone is well nourished / has good status unless clinically defined as deviating from this

Answer 98

For determining nutrition status (or nutrition problems) a comprehensive history may include: 1. › Physical examination - Anthropometric measures (ht/wt, wt changes (how much, over how long, why) - Fat / muscle stores 2. › Intake - Diet history / food records / … ie some kind of assessment of dietary intake, comparing this to known reference standards - RDIs for age/sex - Estimated protein / energy requirements - ?AGHD/ food groups 3.› Biochemistry - Eg iron status, and many other parameters – variable 4.› Functional status - Ie what is the person able to do, compared with norms, and contributors to any changes › Medical history and disease state

Answer 99

Screening and assessment tools available for clinical application: 1 - screening tool may be decision tree for referral to dietitian – often done by nursing or other allied health eg MST 2 - Assessment tools – require dietitian to implement and interpret – used to diagnose malnutrition in hospitals 3- MNA (mini nutritional assessment) 4 - SGA (subjective global assessment)

Answer 100

1 - Nutritional crisis, food insecurity à involuntary nutritional inadequacy and starvation (famine) 2 - Illness eg malabsorption of nutrients, drug nutrient interactions, altered metabolic fate of nutrients, nausea, vomiting, anorexia, cancer cachexia, GIT disorders (eg motility, enzyme dysfunction, enteropathies, strictures/blockages), etc 3- Anorexia 2o anxiety/stress, altered appetite 2o eg drugs (ADHD meds, etc) 4- Lack of knowledge about good nutrition 5- Eating disorders 6- Drug dependence eg alcohol 7- Increased requirements eg post trauma / surgery, some cancers

Answer 101

- Specific nutrient(s) – quite common! - Energy - Protein-energy – common in elderly and marginalised groups

Answer 102

› In children 1- Growth retardation / stunting 2- Delayed developmental milestones 3- Diseases of inadequate specific nutrients eg rickets

Answer 103

1- Muscle wasting 2- Increased risk infection / pressure wounds 2o compromised immune function 3- Longer healing times 4- Increase risk hospitalisation and length of stay 5- Death 6- Nutrient specific diseases eg osteoporosis, anaemia, etc 7- Diminished cognitive performance 8- Decreased physical ability 9- Decreased quality of life

Answer 104

1› Massive cost in human terms in some developing countries 2› High personal cost to person in terms of quality of life, their family and friends, and also to health system 3› Rate of malnutrition in Australian hospitals reported up to 50% 4› Risk malnutrition increases with length of stay 5› ~50% nursing home residents malnourished

Answer 105

1› Elderly esp with co-morbidities - Eg Parkinson’s, polypharmacy, dementia, COPD 2› Unwell - Disabled, housebound - Chewing / swallowing problems - Cancers 3› Socially disadvantaged, including children from low SES backgrounds, despite often being overweight 4› Young people esp women with restrictive eating practices 5› Population with psychiatric disorders

Answer 106

many of | whom survived the camps only to die when refed – usually of cardiac failure

Answer 107

In starvation, physiology alters 2degree lack of glucose/energy 1› Insulin levels drop, glucagon increases… glycogen stores utilised and biochemical shift to gluconeogenesis initially….. 2› Ketones and FFA become main energy source… (initially low ketone body use peripherally to conserve protein/muscle breakdown) 3› Eventually loss of lean muscle mass occurs 4› Biochemical stability of serum levels of Mg2+, K+, PO4 3- continues, but intracellular stores (where you would expect the greater concentration) become depleted as a result of the fat/protein catabolism, and intracellular volume also shrinks 5› Vitamin losses may become critical, particularly thiamine 6› Urinary losses of minerals such as K+ and Mg2+ are reduced during starvation

Answer 108

Sudden shift from catabolism to anabolism 1 Influx of CHO – becomes major fuel – hyperglycaemia may occur and insulin induction may lead to a biochemical cascade 2 › Na+-K+ ATPase transporter stimulated by insulin - à dramatic shift of K+ from extra- to intra-cellular space with H2O shift following (osmosis) - Also transports glucose into cells - Water follows by osmosis 3 › Insulin stimulates glycogen, fat and protein synthesis – requiring phosphate, Mg2+ and cofactors (eg thiamine) 4 End result? Decreased serum K+/Mg2+/PO4 3-

Answer 109

› Coenzyme forms: thiamin pyrophosphate (TPP) thiamin triphosphate (TTP) › Coenzyme for decarboxylases eg: - Oxidative decarboxylation - In glycolysis and TCA cycle - Of branched chain amino acids - Transketolase reactions in the pentose phosphate pathway

Answer 110

cause beri beri

Answer 111

it is an importan co-facto in Kreb cycle-prosthetic group on pyruvate dehydrogenase

Answer 112

› RDI 1.1-1.2mg / day (adults) | › Max ~30mg in body

Answer 113

› Sources - In small but sufficient quantities in most nutritious foods - High in pork products, sunflower seeds, pasta, bread (mandatory fortification in Aus)

Answer 114

› Biochemically fragile - not stored long term – consumed or excreted › In food, may be destroyed by heat, leached into cooking water (water soluble) › Half-life: 9-18d

Answer 115

``` 1› Inadequate intake 2› Chronic alcoholism - Thiamin absorption is impaired - Decreased food intake - Increased excretion 3› High (inadvertant) intake of thiaminase eg raw fish 4› Compromised nutritional intake for a period of time eg some groups of hospitalised patients ```

Answer 116

``` Peripheral neuropathy 1› longest nerves affected first long limbs – legs 2› loss of sensation Enlarged heart, cardiac failure Weight loss Muscular weakness - can’t walk, foot drop Poor short term memory ```

Answer 117

Acute Oedema Raised jugular vein pressure

Answer 118

› BUT not usually seen with Beri beri - ?WE/KS more common in those who are less active - Most commonly seen in alcoholics

Answer 119

› Symptoms may include: - Wernicke’s encephalopathy - Ocular disturbances (eg nystagmus), ataxia (unsteady stance and gait), confusion, hypothermia, apathy, coma

Answer 120

- Korsakoff’s syndrome - Amnesia - Confabulation › Other possible symptoms: hypotension, tachycardia, hypothermia, progressive hearing loss, epileptic seizures, dementia

Answer 121

PO43- shift 1 › In starvation, PO4 3- may stay in N range 2› Insulin stimulates cellular uptake of PO4 3- > potentially profound hypophosphataemia - NB PO4 3- required for generation of ATP - Sudden large drops in PO4 3- or a drop below ~.5mM may produce refeeding symptoms - eg rhabdomyolysis, leucocyte dysfunction, respiratory failure, cardiac failure, hypotension, arrhythmias, seizures, coma, sudden death

Answer 122

potassium K+ shift 1› NB major intracellular cation 2› In starved state serum levels may remain in N range 3› In refeeding, taken up into cells as they increase in volume and number 20 effects of insulin 4› Severe hypokalaemia -> derangements in membrane potentials -> eg arrhythmia and cardiac arrest

Answer 123

1› Also predominantly an intracellular cation 2› Important co-factor in many enzyme systems (including oxidative phosphorylation, ATP production) 3› Necessary for structural integrity of DNA, RNA, ribosomes 4› Deficiency has an effect on membrane potentials and can lead to cardiac dysfunction and neuromuscular complications

Answer 124

1› After starvation, glucose intake suppresses gluconeogenesis thru insulin release 2› XS glucose often leads to hyperglycaemia then to osmotic diuresis, dehydration, metabolic acidosis, ketoacidosis 3› XS glucose may also lead to lipogenesis, fatty liver, increased CO2 production and respiratory failure.

Answer 125

Returning CHO to system can have profound effects on sodium and water balance › -> rapid decrease in renal excretion of sodium and water › If significant fluids are provided for repletion (eg IVF) in order to maintain normal urine output, fluid overload may develop -> - Congestive cardiac failure, pulmonary oedema, cardiac arrhythmia

Answer 126

› ‘severe hypophosphataemia, sometimes accompanied by severe hypokalaemia or hypomagnesaemia, of both; vitamin deficiencies (particularly thiamine); fluid or glucose intolerance or both; and attendant complications which may arise when malnourished patients are refed – orally, enterally or parenterally’….

Answer 127

1› Changes in electrolyte balance, esp Mg2+, K+, PO4 3- 2› Vitamin deficiencies, esp B1 3› +/- Sodium/fluid retention 4› +/- Difficulty metabolising glucose This may lead to major metabolic/physiological consequences, including death

Answer 128

› No/little food intake >5 days, 1- especially on a background of illness / malnutrition 2- BMI

Answer 129

1› Thiamin pre-feeding and for at least 3 days 2› Multivitamin 3› Feed slowly – start with small amounts even if hungry 4› Monitor electrolytes pre-feeding and daily - Replete (K/Mg/PO4)as required and only increase intake if stable - Monitor at least a week – signs of refeeding may not appear until a number of days after commencing refeeding 5› Not huge intakes of either fluids or CHO until stable

Answer 130

› Extremely low BP when admitted to hospital › Provided parenteral thiamine › Provided Vit K, multivitamin with trace elements daily › Day 2 – 61kg (had been 80) – almost 20% body weight loss in 6 weeks! › BGL 5.11mM, creatinine 0.1mM, Na 128mM, K 3.0mM; urine sample – traces ketones › 2l IVF and 1.5l oral fluid, with dextrose added after the first thiamine dose › Presented with overt signs of Wernicke’s – may have been aggravated by food provided shortly after found › Presented with gaze palsy – resolved within 12h of admission (thiamin) › Seen by psychiatrist – some paranoia noted (possibly the only sign of Korsakoff’s) › Day 3 – severe foot pain ?axonal peripheral neuropathy of B1 deficiency (Likely also thermal effects) › Day 4 creatinine level 0.06mM (renal function improving) › Day 6 - tachycardia › Day 10 – flown home to Brisbane - Nystagmus, Mg 0.77mM (repleted) › Day 16 – EEG – some abnormalities › Day 23 – EEG – abnormalities resolved › After 5 weeks – discharged – slight nystagmus persisted at least 5y later

Answer 131

› Feeding before repletion may have exacerbated B1-deficiency symptoms › Overaggressive rehydration may have caused mild heart failure › No PO4 3- blood testing available in Nepal in 1992

Answer 132

``` › Urine Therapy (urotherapy) diet › Paleo › Gluten free › Organic / ‘clean’ eating › Vegetarian › Vegan › ‘I quit sugar’ › VB6 (vegan before 6pm)/ Chegan (cheating vegan) › Clay Cleanse › South Beach, Blood Type, Sandra Cabot,…. › …… ```

Answer 133

› Healthy › ‘clean’ eating › Weight management › Fountain of youth › ‘a magic bullet’ › Ethical reasons › Religious reasons › A friend of a friend’s sister told me it worked for her…. › Doctor Google › Traditional wisdom may appear to have let them down › Marketed well › Mystical › beautiful Fear mongering - Eg butter vs margarine….. Margarine is evil - Margarine was originally made to fatten turkeys but it killed them instead NO - Eating butter increases absorption of micronutrients HUH? - Margarine is high in trans fatty acids – DEPENDS - Margarine is only one molecule away from plastic NO - Butter is natural so it is better for you (arsenic is also natural!!)

Answer 134

``` › Increased yields › Second crop / season › Drought resistance › ‘bug’ resistance › Physical properties (eg wheat – gluten) › Increased antioxidants › Altered macronutrient ratios › The next big thing! › Increased shelf life › More / less / altered distribution fat (eg beef) › Climate change › Scientific evidence eg p/u oils ```

Answer 135

``` › Perceptions of healthiness › Multiculturalism › Changes in kitchens / appliances › Advertising › ‘time poor’ / convenience › Increased shelf life – shop and pantry › Global village › Organic / locavore › Anti-animal cruelty / ethical › Masterchef, MKR, etc ```

Answer 136

› Whole food groups missing › Supplements required › Charismatic celebrity endorsement › Promise of a quick fix › Miracle ‘cure’ – if it sounds too good to be true, it is! › Pseudo-science or a good dose of good science that is then taken off track › Fear mongering

Answer 137

› 2013 – Google – most searched for weight loss method › Picked up and championed by Pete Evans in Aus › ‘caveman’ diet – akin to prior to agriculture / animal domestication - What did a ‘caveman’ diet look like? - 25% animal derived energy in Gwi people of Southern Africa - 99% animal derived in an Alaskan population › Claim we have been unable to adapt to changes in food supply….modern food supply is the underlying reason for obesity, diabetes, cardiac disease, … and those on paleolithic diet should therefore live longer and be more healthy › Avoid – grains, legumes, dairy, sugar, processed oils and foods, alcohol, coffee

Answer 138

Paleo diet – for and against | ›

Answer 139

CAVEAT: strict GF diet essential for some…. those with Coeliac disease – not a lifestyle choice! There are also those with wheat allergy who must strictly avoid wheat-containing foods, and those with severe intolerance to gluten who need to limit gluten to manage symptoms. These are NOT the groups discussed in the next slides

Answer 140

› Allergy – IgE immune modulated › Intolerance – non-immune – NS involved › Food aversion – often previous bad experience / association; taste/texture aversion?

Answer 141

``` › Coeliac Disease › Wheat allergy › Exercise-dependent, wheat-induced anaphylaxis › Gluten intolerance › You have been told it is good for you (NB below are NOT true) eg - gluten is indigestible - Not part of paleo diet - Causes autism - Improves athletic performance: ```

Answer 142

› Naturopath – many ailments – usually without proper testing › Celebrities espousing the benefits eg Miranda Kerr, Gwynyth Paltrow, Miley Cyrus,

Answer 143

``` › Low FODMAP developed to manage symptoms of IBS not a weight loss plan › If you cut out the FODMAPs what else are you removing? Is the removal of other chemical components from the diet or the FODMAPs themselves assisting with symptom management? › This should also be a test diet, not a long term diet ```

Answer 144

› Very difficult 20 years ago to find GF alternatives to staples such as bread / pasta – alternatives often not palatable › Driver of food supply change – high demand, whether by choice or necessity: - Supermarket alternatives – big business - REALLY important for those with real health issues!!!! - Coles / woolies have own GF ranges - Usually MUCH more expensive than gluten-containing alternative - BUT a huge range and many are either v similar to gluten-containing alternatives or taste good in own right - Health food stores

Answer 145

› Often low fibre › ‘special dietary food’ therefore no mandatory fortification of flour with folate, B1, I – many on GF diet are deficient › Often highly refined, poor nutrient density, high GI › Seen as healthy so more processed food eg biscuits may be consumed › Ironically many Coeliacs would LOVE normal bread!!! And compliance with GF diet is often poor

Answer 146

warning signs include › Expensive to follow - Ingredients may be expensive eg large amounts meat on paleo, making organic produce a ‘must’, - SUPPLEMENTS….. Usually marketed by the person promoting / designing the diet › Outlandish promises….. If it sounds too good to be true, it probably is! › Whole food groups missing often eg grains and legumes – difficult to get nutritional adequacy › Usually elements of truth which make the diet appear plausible eg decrease refined/processed foods or sugar and encourage otherwise healthy lifestyle › Usually promoted by charismatic people who make is sound like the answer to all things healthy

Answer 147

› A hole in the hip pocket! Might be the least of your worries › Nutritional inadequacy – the results may not be seen in the short term, but on a dairy free diet, what are the risks for osteoporosis / fractured bones, (esp hip) in the future??? › Excess of undesirable nutrients eg saturated fat. ??? Long term risk for eg cardiac disease? › Eating disorder or at least disordered eating and a lifetime bad relationship with food??

Answer 148

epigenetic, environment and genotype | epigenetic is seen when the phenotypic variation persists even when genotype and environment are controlled for

Answer 149

Epigenetics: a system of gene regulation involving heritable changes in gene expression that occur independent of changes to the DNA sequence

Answer 150

Epigenetic gene regulation is fundamental to the life of all eukaryotic organisms: it creates phenotypic variation not only within an individual, but also between individuals

Answer 151

Epigenetic gene regulation is a binary system: “On” or “Off” Epigenetic states are probabilistic – every locus has some probability of being silent

Answer 152

The human genome is ~3.1 x 109 bases long – over 2 metres worth in every human cell! Eukaryotic DNA is packaged into chromatin.

Answer 153

light stain, active

Answer 154

silent, dark stain

Answer 155

DNA+associated proteins and RNAs

Answer 156

Nucleosome packaging determines chromatin structure and transcription state. in active locus, there is molecule modification on histone protein tail in silent locus, it is different modification that keep histone pack together. e.g methylation of CpG, inactive the gene

Answer 157

Epigenetic modifications allow cells with precisely the same genomes to adopt a multitude of phenotypes based on the activity of some loci and the silencing of others Cell differentiation is epigenetic gene regulation par excellence ~25,000 genes in human genome – each cell type uses only a proportion, and the remainder are silent

Answer 158

A cell’s epigenotype – the pattern of active and silent loci – is set during differentiation Once set, epigenotype is generally stable

Answer 159

Errors in this process have the potential to be maintained for a lifetime, and sometimes even transmitted to future generations

Answer 160

t.telomere, centromere and telomere are heterochromatin

Answer 161

Epigenetics is interposed between genes and environment Epigenetic modifications mediate genome function and are responsive to environmental cues e.g. cellular, organismal and external The probability of epigenetic errors may be influenced by the environment and the most vulnerable time is during our development when cellular epigenotype is set

Answer 162

– the basic unit of chromatin ~146 bp of DNA wrapped in 1.65 left-handed turns around a histone octamer – same in all eukaryotic genomes Histone octamer consists of two copies each of the core histones H2A, H2B, H3, and H4 Adjacent nucleosomes are joined by a stretch of free DNA termed "linker DNA" to which another linker histone (H1) binds

Answer 163

there is lots of possible combination, maybe a histone code?

Answer 164

activation: acetylated H3K9 repression: methylated H3K9 activation: acetylated H3K14 repression: methylated H3K27 activation actylated H4 (K generally) repression: sumoylation (K generally) activation: methylated H3K4 repression: methylated H4 K2O activation methylated H3K36

Answer 165

model 1: chromatin structural change (e.g. histone tail modification) model 2: inhibit binding of negative-acting factor model 3: recruit positive acting factor

Answer 166

* Covalent modification of DNA itself * Addition of a CH3 group to C5 on cytosine * Does not alter Watson-Crick pairing, or the helical structure of the DNA * Added by DNA methyltransferase, with the CH3 group donated by S- adenosyl methionine * In mammals occurs primarily at cytosines in a 5’-CG-3’ context – “CpG methylation”

Answer 167

• The idea that CpG methylation could represent a mechanism of cell memory arose independently in two labs in the mid 70’s • CpG dinucleotide is self-complementary – this led to the proposal that patterns of methylated/unmethylated CpGs could be copied when cells divide, providing a mechanism for mitotic inheritance of epigenetic patterns

Answer 168

5-mC is more mutable than C (deaminates to U)

Answer 169

CpGs in constitutive heterochromatin CpGs in retrotransposons and their relics CpGs in introns and exons Most intergenic DNA CpGs

Answer 170

• Originally detected in 1983 as the fraction of vertebrate DNA that was cleaved by the DNA methylation-sensitive restriction endonuclease HpaII • When promoters started to be mapped it was noted many were in GC-rich regions. It is now known that ~65% of CpG islands mark gene promoters – about 60% of genes have CpG island promoters • CpG islands often found at housekeeping genes – lack of methylation important in keeping genes active • Definition now computational: – GC content ≥50% – length >200 bp – Obs/Exp CpG > 0.6

Answer 171

CpG methylation is not generally used for dynamic gene regulation – it is a mark of permanent silence (once you’re methylated you’re likely to be off for good!)

Answer 172

ACTIVE GENE PROMOTERS: no DNA methylation, H3K4me, H3K9Ac histone modifications ACTIVE GENE BONEDY: yes DNA methylation, H3K36me histone modifications SILENT GENE PROMOTERS-NORMAL CELLS: sometimes (~8%) DNA methylation, H3K27me histone modifications SILENT GENE PROMOTERS-CANCER CELLS: often DNA methylation, H3K27me histone modification OTHER SILEN SEQUENCES E.G. CENTROMERIC, RETROTRANSPOSON: yes DNA methylation, H3K9me histone modifications

Answer 173

Epigenetic silencing involves a complex interplay between DNA methylation, histone mods, and chromatin proteins If histone mods can be said to “close the door” on transcription, CpG methylation is they key that “locks” it CpG island methylation is the most reliable marker of stable transcriptional silence

Answer 174

in active chromatin (which is euchromatin): loosely packaged, replicates early, bound to TF and RNA polymerase, histone modifications: acetylated H3K9, methylated H3K4, methylated H3K36 (gene body), and no DNA methylation in silent chromatin (heterochromatin) - tightly packaged, replicate late, bound to heterochromatic protein like HP1, histone modification: methylated H3K(, methylated H3K27, there will be DNA promoter methylation

Answer 175

• Gene regulation and cell differentiation * X-chromosome inactivation * Mobile element (retrotransposon) silencing * Position-effect variegation * Parental imprinting

Answer 176

The Barr body – the inactive X-chromosome

Answer 177

One of the two X chromosomes in therian females is silenced to ensure the correct dosages of genes on the X Once silenced in early development, the inactive X is maintained through cell division – giving clonal patches of X-inactivation Silencing is random …. Almost. In the placenta of eutherians and in all tissues of marsupials, the paternal X is always silenced. Calico cats are only ever female – if you have seen a male, he probably had XXY trisomy!

Answer 178

Barbara McClintock discovered mobile genetic elements in maize (corn) in the 1940s. She recognised that mobile elements could silence (or sometimes activate) the loci they landed near, in a mosaic and heritable fashion – and called them “controlling elements”. We now know that mobile genetic elements – transposons and retrotransposons – make up 50% of our own DNA!

Answer 179

Retrotransposons take up almost half our genomes - having amplified themselves via retrotransposition over eons They are dangerous – their retrotransposition can cause insertional mutations Hence … They are MAINLY heterochromatic – in fact, DNA methylation may have evolved to keep them silent They can control the expression of nearby genes – either by heterochromatising them, or by activating and causing transcriptional interference

Answer 180

Controlling elements display behavioural features now recognised as characteristic of epigenetic phenomena: - Mitotic heritability (stable throughout life) - Meiotic heritability (stable between generations) - Inter-individual variability - Phenotypic mosaicism

Answer 181

* Epigenetics is the primary system of gene regulation in eukaryotes * Epigenetic modifications change gene transcription state – active or silent * Epigenetic modifications involve covalent changes to DNA and histones, and recruitment of silencing or activating proteins * Epigenetic states can be modified by environment

Answer 182

* Maintenance, repair, growth of tissues * Formation of skin, hair, nails * Production of plasma proteins * Synthesis of antibodies, receptors, enzymes, hormones, neurotransmitters, channels & pores * Milk protein in lactation

Answer 183

PROTEIN IN DIET--(digestion protein converted to a.a)-> a.a. metabolism in tissues -> urea synthesis for excretion the amino acid metabolism in tissues ---dynamic flow, constant turn over -> body protein

Answer 184

e.g. e.g. 100g of protein in diet, the trpsinogen secrete in pancreas get activated form trpsin in the gut, the protein is converted to peptides by trypsin, then peptide break down into a.a. the peptide can also converted in the gut epithelium into a.a. then a.a. (160 g) absorbed and transport via portal vein to liver. . liver convert the a.a. to urea, liver protein and plasma protein. in the fecal there is 10g of protein there is 70g of endogenous protein. L7

Answer 185

After a meal containing protein: – Portal blood ↑↑ amino acids – Systemic blood smaller ↑ amino acids – Liver regulates the fate of amino acids (50% -> urea or keto acids; 14% retained in liver; 6% secreted as plasma proteins; 23% secreted as free amino acids)

Answer 186

amino acid-> keto acid->TCA cycle->CO2+H2O+energy or amino acid-> amino group-> urea-> urine

Answer 187

body protein turnover go to 1. muscle 2. secreted gut protein 3. protein synthesis and degradation 4. white cell 5. liver 6. skin

Answer 188

floating a.a. everywhere, last b/t meal not b/t days.

Answer 189

a.a. different to each other due to side chain- the charge, size, 150 different a.a. we eat, only use 20 a.a. different a.a. join together by peptide bond to form protein

Answer 190

1. Histidine (His) in children only 2. Valine (Val) 3. Leucine (Leu) 4. Isoleucine (IIE) 5. Lysine (Lys) 6. Methionine (Met) 7. Threonine (Thr) 8. Phenylalanine (Phe) 9. Trptophan (Trp)

Answer 191

1. tyrosine 2. glycine 3. alanine 4. cysteine 5. serine 6. aspartate 7. asparagine 8. glutamate 9. glutamine 10. argine 11. proline

Answer 192

limiting amino acid= essential amino acid that is in low concentration such that it limites the rate of protein synthesis

Answer 193

Dietary intake N = loss of N from the body B = I – (U + F + S) = Intake - Losses balance= N intake - ( urinary N+faecal N+skin,etc losses) urinary N include urea ammonium and creatine

Answer 194

``` more intake than lost occurs in: – Anabolic states – Growth – Pregnancy – Convalescence – Excess energy intake – Muscle training – Androgen, anabolic steroids – Growth hormone – Switch from low to high intake (temporary) ```

Answer 195

``` occurs in: – Injury – Surgery – Stress – Infections – Cortisol – Diarrhoea – Burns – Bleeding – Proteinuria – Insufficient protein intake – Insufficient dietary energy i.e. catabolism ```

Answer 196

The diet should provide the essential amino acids and enough amino acid nitrogen to synthesise the non-essential amino acids. - Minimum requirement is 25g protein/day if all amino acids are present and in their optimal ratio

Answer 197

Australia RDI: 64g (men) (-52g) 46g (women) (-37g) (-EAR) EAR=estimated dietary requirement in UK RDI is 10% of dietary energy in USA RDA: 56g (men) 44g (women) (0.8g/kg BW) usually we eat ~100g/day

Answer 198

Two ways to estimate protein requirements 1. Factorial Method 2. Nitrogen Balance Method

Answer 199

Assumes that on a diet devoid of protein: Sum of losses of N = obligatory losses ≡ min. requirement a. Urinary losses: 37mg/kg BW/day in adult male b. Faecal losses:12mg/kg BW/day in adults c. Skin losses+ minor routes: 6mg/kg BW/day a + b + c = 54mg/kg

Answer 200

Conversion Factor = 6.25 | Proteins are 16% N, so to find out quantity of protein from N, x 100/16

Answer 201

Conversion factor N x 6.25 = amount of protein = 0.34 g protein/kg/day (as N = 54 mg/kg) BUT assumes dietary proteins are used with 100% efficiency

Answer 202

- even egg protein not used for 100% efficiency - assume 70% efficiency for egg, min. req.for egg protein =0.49g/kg/day (0.34x100/70) - other protein even less efficiently utilised, min req. of mixed diet=0.75g/kg/day

Answer 203

- finds the minimum amt of protein needed to restore N equilibrium - add different levels of protein to a protein-free diet - measure improvement in N balance - lowest level that achieves 0 balance= minimum protein requirement - done in rats - the results shows that as protein increase in diet, the urinary N increase and vice versa - however the endogenous excretion plateau and doesnt go 0, because its the obligatory losses always lose N even no protein taking in - the study found that the actual requirement for N equilibrium is much higher than theoretical requirement

Answer 204

• Protein quality depends on:- – The amino acid make-up – The digestibility – The amount present

Answer 205

1. Digestion and absorption rate of native • Animal protein: 90% • Vegetable protein: 60-70% 2. Limited protein digestibility due to: • Protein conformation effects • Interaction with metal ions, lipids, nucleic acids, cellulose • Individual differences

Answer 206

using PROTEIN DIGESTIBILITY-CORRECTED AMINO ACID SCORE (PDCASS)

Answer 207

definition of parameters for assessment of protein quality based on animal experiments. in calculating the PDCAAS value, only digestibility is determined by means of animal experiments

Answer 208

weight gain (g) per gram of protein ingested

Answer 209

[(nitrogen absorbed from food)/(nitrogen ingested)] x 100

Answer 210

[(nitrogen used for tissue formation)/(nitrogen absorbed from food)] x100

Answer 211

true digestibility x BV

Answer 212

[(mg of limiting amino acid in 1g test protein)/(mg of the same amino acid in the reference pattern)] x true digestibility

Answer 213

L7 = % a.a.in test protein/ % corresponding a.a. requirement X [Nuptake-(Nfaeces-Nfaeces endogen)]/Nuptake X100 PDCAAS based on - amino acid content - true digestibility - supply of essential amino acids in amounts adequeate to meet the amino acid requirement of 2-5 yr old child

Answer 214

Highest possible score = 1.0 A score of 1.0 means that after digestion of the food protein, it provides per unit of protein, 100% or more of the essential amino acids required by a 2-5 yr old child. Score above 1.0 is rounded down to 1.0, because amino acids supplied in excess of those required for protein synthesis would be eliminated from the body or stored as fat.

Answer 215

• Analyse food for nitrogen content • Calculate protein (N X 6.25) • Analyse for essential amino acid content • Calculate amino acid score (AAS) AAS= % a.acid in test protein/ % corresponding a.acid requirement • Determine digestibility =[Nuptake – (Nfaeces – Nfaeces endogen)] /Nuptake X 100 • Calculate PDCAAS = AAS X true digestibility

Answer 216

limiting maize= limiting amino acid is trptophan limiting wheat=limiting amino acid is lysine limiting beef= limiting amino acid are methonine/cystein limiting soy bean = limiting amino acid are methionine /cystein

Answer 217

Supplementary value = the capacity of a protein to make good the deficiency of another Eg. Soy bean (low methionine) + rice

Answer 218

Postnatal development, GIT function and energy balance all affected

Answer 219

Microbes are not distributed uniformly. Transit time, available nutrients, physico-‐chemical proper?es and an?microbial secre?ons influence which species can live and where.

Answer 220

Microbial metabolites and MAMPs are the interac?on currency. These change with microbiome composi?on and ac?vity. Diet can induce these changes.

Answer 221

Gut microbiome of all mammals is broadly similar (we can use animal models). Gut microbiome differs in species composi?on even between individuals of the same species (interpreta?on of paNerns is complex).

Answer 222

Gut microbiome is a factor in diseases of complex e?ology. Evidence that it may represent a useful diagnos?c tool. Evidence that it may represent an interven?on target.

Answer 223

1. small hindgut-fermenting mammalian herbivores e.g. guinea pig and koala, Cecum and/or colon developed as large, fermentative organ. 2.large foregut-fermenting mammalian herbivores e.g. sheep and kangaroo. Stomach developed as large, fermentative organ. Small intestines also developed. these two types of herbivores have High nutritional dependence on microbes. 3. mammalian carnivores e.g. dog. Stomach developed as larger, digestive organ Less nutritional dependence....BUT microbe matter

Answer 224

``` Gut microbes are in?mately associated with our largest endocrine, largest immune and second-‐largest neuronal systems. - What we are made of Microbe cells (~ 1014) Our cells (~ 1013)->1-‐2% of our biomass >99% of the genes in our body ``` - How we differ Morphotype Physiotype Immunotype->Weight gain or loss varies in people with comparable diet and exercise. - How we manage health Diet Vaccine/An?bio?c Pharmaceu?cal Exercise->Drug and immune response vary in ways that are not accountable for by gene?c differences. We cannot understand metabolic or immune disorders without knowing the influence of microbiota.

Answer 225

What difference does the presence of microbes make? Most animals survive without microbes BUT have a very different phenotype. in normal mouse: fucose on epithelial surface, intestinal vascularisation (capillary formation), adherent mucin present, thick mucin barrier in colon in germ free mouse: surface carbohydrates are different, normal tissue development does not occur, thinner mucin layer, lack firmlt adherent mucus THM: Microbes impact the nature of the interface between what we eat and the rest of our body e.g. absorp;on efficiency and barrier func;on.

Answer 226

Microbes influence host nutri

Answer 227

Gut microbiome: the metagenome of the resident GIT microbes in an individual. Microbiome distribu?on is influenced by host anatomy and ac

Answer 228

The gut microbiome is shaped by: • Flow rate (sets growth rate) • Presence/absence of oxygen, acids, bile salts and an?microbials • What compounds we eat, how effec?vely we digest and absorb them, what nutrient sources we secrete into the gut

Answer 229

there is low to moderate bacterial numbers in ileum, very high bacterial numbers in the colon. - Our gut microbiome lies at the interface between our environment and our body system. - Our gut is VERY tightly connected to endocrine, immune and CNS functions - Microbe potential to influence environmental state. Microbe potential influence perception of environmental state. Microbe potential to influence response to environmental change. - different interactions with microbes in different places.

Answer 230

1. Stomach – Rectum gradient: Increasing microbial cell concentra?on. 2. Centre – Edge gradient: The epithelial zone is typically different to lumen.

Answer 231

The outcomes of interaction with our microbiome depends on where the interaction is occurring. 1. in the stomach, predation 2. in the ileum, competition and commensalism 3. in the colon, its commensalism and co-operation. 4. through the whole diegestive gut e.g. stomach to colon its amensalism

Answer 232

Food intake changes with availability and eating habits -> microbial growth and metabolism -> metabolites (SCFA) or molecular patterns (MAMPs) -> then these molecules goes to the PRIMARY INTERSECTION POINTS (intestinal interface), Barrier function changes with enterocyte health modifies signal interface, co-evolved (host and microbe genes), Expression patterns of pathway components change ->modifies signal response - there are 5 primary outcomes: 1. lymphocyte maturation (SCFA+MAMPs) 2. Epithelial health (SCFAs) 3. neuroendocrine signalling (SCFAs) 4. PRR mediated signaling (MAMPs) 5. GPR mediated signaling (SCFAs) the emergent outcomes can be result from the primary outcomes 1. inflammatory tone, 2. energy balance 3. gut motility 4. appetite regulation

Answer 233

1. our diet can impact on the gut microbiome (environement impacts microbiota composition) 2. the gut microbiome can impact on our physiology, such that the microbial activity (SCFA production) impact on the enterocytes: proliferation and function, the microbial presence (molecular patterns) can impact on the immune cells: differentiation and immigration.they can also affect the endocrine cells: regulatory response. the human health derives from interactive effects between our environment and gut microbiome. 3. our diet can affect our physiology, environment impact our nutritional state and stress 4. our physiology can impact on gut microbiome -Disease states may result from disturbance to the normal host-‐ microbiome interac?on DYSBIOSIS

Answer 234

Nutrient sources maMer to Bacteria too -‐ why? Different requirements to access it (enzymes to solubilize or catabolise) Different energy yield (ATP produced impacts how much available for growth) ‘Nutri?onal value’ – nitrogen and sulfur not in sugars; phosphorus not in protein Nutrient concentra

Answer 235

Different requirements to access it (enzymes to solubilize or catabolise) Different energy yield (ATP produced impacts how much available for growth) ‘Nutri?onal value’ – nitrogen and sulfur not in sugars; phosphorus not in protein

Answer 236

Nutrients get into a cell by one of: (1) diffusion; (2) facilitated diffusion, or; (3) ac?ve transport Diffusion processes operate against concentra?on gradients -‐ threshold Ac?ve processes expend energy -‐ reduce energy available for growth

Answer 237

t | in the microbial food web, there are multiple bacterial involve in the 1 certain pathway

Answer 238

1. Metabolites are products of microbial metabolism: (include: methane, CO2, Butyrate, propionate, acetate, cresols, H2S, trimethylamine, modified 'drug' derivatives) • Produced during growth (primary metabolites) • Produced by non-growing, but active cells (secondary metabolites) • Produced accidentally by active cells (co-metabolites) 2. Microbe-associated Molecular Patterns (MAMPs) are distinctive components of the microbial cell: (include: peptidoglycan, flagellin, lipopolysacchride, lipid A core and polysacchride) • Part of the cell, present in live, dormant or dead cells • Unique to microbes – not in the host • Can be differentially present (especially flagellin)

Answer 239

There are two main ways in which composition of the microbial community is predicted to make a difference. for metabolites: 1. speicies abundance, different bacterial species, species A produces butyrate, species B produces acetate, species C produces methane 2.cell activity pattern: different cell activity. activa VS dormant, activity on food A vs activity on food B for microbe-associated molecular patterns (MAMPs): 1. species abundance distribution: different bacterial species: Gram+ VS Gram -, type of flagellin, types of polysacchride 2. cell activity pattern: different gene expression: flagella on/off, capsule on/off How different the species are, also influences how much any change in relative abundance or activity matters

Answer 240

Culture-‐based vs DNA-‐based view of microbial diversity 1. culturing Only samples cells that remain live and viable aoer handling protocol Only samples what grows to detec?on limits under culture protocol Only dis?nguishes what is different under analysis protocol Rela?ve abundance of each type reflects colony-‐forming units, not individual cells 2. high throughput sequencing Only samples cells that yield DNA aoer extrac?on protocol Only samples what is targeted by primers under PCR protocol Only dis?nguishes what has different 16S rRNA under analysis protocol Rela?ve abundance of each type reflects amplifica?on success and gene copy number, not individual cells

Answer 241

1. 3 Patients each contributed 7 samples (cecum, ascending, transverse, descending, sigmoid, rectum, stool) 2. Each column on the figure represents one sample (the indicated one is the stool sample from patient C). 3. Each row in the figure represents a single phylotype. The relationship of that phylotype to all others is shown in the tree on the left (the indicated ones are members of a subgroup within the Firmicutes - colour-coded orange). 4. For each sample dataset the greyscale represents the abundance of that phylotype in that sample (the circled one had 5-10 reads in the ascending bowel sample of patient C). 5. Adding all rows gives a total of 395 phylotypes seen in the study: -> no one sample [vertical column] had all of them 6. Some phylotypes were completely absent from all samples from one patient (red box): -> the set of phylotypes in each patient is different. 7. In each patient more phylotypes were seen in the stool sample (red arrows) than in any other sample: -> the pattern of diversity differs between sample sites

Answer 242

``` Firmicutes Bacteroidetes Verrucomicrobia Proteobacteria Actinobacteria Fusobacteria ```

Answer 243

p21 look at it

Answer 244

there is more bacteriodetes and firmcutes. p22

Answer 245

We have a dis

Answer 246

gut microbes are not necessory AND sufficient to cause any of these diseases but they necessary in some contexts AND they are sufficient in some contexts. 1. Evidence from cross sectional studies The major phyla, Bacteroidetes and Firmicutes show different distribu?on in obese vs. lean Successful weight loss diets shio both microbiome and obesity 2. Obesity phenotype is transmissible

Answer 247

Varia?ons in microbial community composi?on can lead to different outcomes BUT associa

Answer 248

``` There are ‘bad bugs’ in some diet-‐induced dysbioses Each HFD induces microbiome change. Saturated fat consistently induces disease. Problem: Dysbiosis at the intes?nal interface. High saturated fat diet results in expansion of a pathobiont (sulfate-‐reducing bacteria), impaired gut barrier func?on and localised inflamma?on.P27 T4 ```

Answer 249

TLR4 and NOD1 KO models are essen?ally protected from diet-‐ induced glucose intolerance.

Answer 250

TMAO is a microbiome derived molecule with implica

Answer 251

Diseases that have immunophenotype or energy balance as risk factors effec

Answer 252

1) Targeted interven

Answer 253

Targeted interven

Answer 254

Obesity: Can we improve ability to predict dietary interven

Answer 255

T4 summary

Answer 256

• Growth – protein synthesis > protein degrada4on – childhood growth, pregnancy, lacta4on, recovery from was4ng condi4on – Linear growth need protein deposi4on of bone matrix. • Height determined by gene4c makeup but illness or protein deficiency can influence this. • Also need calcium, phosphorous, zinc and other micronutrients Recovery from wasting conditions = convalescence

Answer 257

• Specific amino acids and amounts required determined by the amount and paOern of amino acids being used for protein synthesis – Collagen: high in glycine and proline, low in leucine and BCAA – Inflammatory response: making glutathione and metallothioneins requires lots of cysteine No fix and amount of amino acid for life, all depend on physiological state.

Answer 258

No specific place for amino acid pool, Inflow: dietary intake, de novo synthesis (non-essential a.a.), protein degradation Outflow: oxidation (contribute to energy requirement, when the a.a. is in excess), other pathways, protein synthesis (major pathway)

Answer 259

``` • Transamina4on • Oxida4ve deamina4on • Gluconeogenesis • Urea cycle • Amino acid biosynthesis When we digest the protein, liver is the first place to see a.a., it holds a lot of amino acid. 50% of the metabolism energy in liver contributed by a.a., main site for uptake a.a. after a meal and catabolism of essential a.a. except BCAA (break down in heart and muscle) ```

Answer 260

• Transamina4on – converts one amino acid into another – catalysed by aminotransferases • Oxida4ve deamina4on – removal of the amino group Transamination: Aminotransferases: transferring amino group on the amino acid from 1. Amino acid to carbonskeletaton to form another amino acid, important for de novo synthesis-> major for non-essential amino acid.

Answer 261

Alpha-keto acid, like a.a. but it is missing amino group e.g. alpha-ketoglutarat, by aminotransferase, amino group is transfer from a amino acid to alpha-ketoglutarate (also know as carbonskeleton) to make another amino acid such as glutamate. This require the co-factor PLP (pyridoxyl 5’-phosphate=active vitamin B6). PAP is an essential in transamination, this is why VB6 is also important. This process is reversible, if too musch glutamate in the body, it reverse to alpha-ketoglutarate to make other amino acid.

Answer 262

• Aminotransferases – cytosol & mitochondria – requires pyridoxal phosphate co-factor – Alanine and aspartate aminotransferases (ALT & AST) Aminotransferases is the enzyme that facilitate this conversion. Found in cytosol and mitochondria. Require PLP as cofactor, e.g. of the aminotransferases are ALT&AST. If too much aminotransferases in the plasma indicate the cell are dying in the liver, releasing the enzyme into the plasma. ALT use the amino group from alanine and add in alpha-ketoglutarate, to form another amino acid alpha-a.a. typical glutamate. Alanine is converted to alpha-keto acid, alpha carbon skeletal pyruvate. AST take amino group from aspartate turn it into oxaloacetate, the oxaloacetate then go into the CREB cycle and contribute to energy production in the cell. Alpha-ketoglutarate and glutamate have key role in amino acid metabolism, facilate interchange between a.a.,, make new a.a. and release carbon skeleton that used for energy

Answer 263

* Glutamate dehydrogenase – Oxida4ve deamina4on of glutamate * Regenerates 2-oxoglutarate • Releases ammoniaàurea • Mitochondria * Reversible reac4on * ATP/GTP inhibit; ADP/GDP ac4vate Oxidative deamination is the removal of the amino group, not transferred. Glutamate dehydrogenase is the main enzyme responsible for oxidative deamination. It is involved in the oxidative deamination of glutamate. It regernerate 2-oxoglutarate, the amino group if final into urea. It occur in the mitochondria and it a reversible reaction. There are different co-factor that inhibit (ATP/GTP) and activate (ADP/GDP) it. E.g. in the fasting state, the glutamate dehydrogenase will increase to liberate alpha-keto acid=oxoglutarate (2), this 2 can also go to creb cycle to liberate energy. The ammonia is excreted through urine. The amine group on glutamate, it can use NAD(P) or NADPH to help to take off the ammonia group to produce the carbon skeleton=alpha ketoglutarate. The ammonium go to the urea, the alpha-ketoglutarate can go to the TCA cycle.

Answer 264

• UNDERNUTRITION – Deple4on of energy (calories, kJ • MALNUTRITION – Serious deple4on of any of the essen4al nutrients • FASTING – Voluntary absten4on from food • STARVATION – Involuntary lack of food • FAMINE – Severe food shortage of whole community • WASTING – Reduc4on of body size, especially musclle from insufficient food, disuse or disease` Undernutrition: generally not enough energy related to the lack of amino acid Malnutrition: overnutrition is a type of malnutrition During starvation, turn to protein to produce energy

Answer 265

• Hypoinsulinemia s4mulates proteolysis • Breakdown of muscle protein to release amino acids – large amount of alanine & glutamine • These are preferen4ally taken up by liver – Small amount of branched chain amino acids During starvation, the insulin level is very low, insulin is an anabolic hormone, response to the nutrients increase in the body. Hypoinsulinemia will stimulate the break down of protein to release amino acid. Large amount of alanine and glutamine released from the muscle and preferentially taken up by liver and break down by liver. There are small BCAA chain is liberated.

Answer 266

• Marasmus • Kwashiorkor they are Protein-energy malnutri4on (PEM) These 2 conditions are conditions of protein-energy malnutrition (PEM) =protein deficiency and energy malnutrition.

Answer 267

• Protein and energy deficit • severe stun4ng of growth and irreparable damage to development • responsible for death of 5.2 mil children

Answer 268

• Protein deficit with energy sufficiency • Poor quality food -high carbohydrate / low protein diet • limits growth and development • leads to oedema, reduced immunity, diarrhoea and death Kwashiorkor is protein deficiency but they have just enough energy, because in the under develop country, education is low, the children on put onto inappropriate poor quality food e.g. high carbs, low protein diet, in children they need more a.a. more protein than adult, poor quality food limit growth and development. This lead to oedema (not enough protein e.g. albumin in the blood, change the osmotic pressure, some fluid from the cell and EC space go into the blood), reduced immunity, diarrhea and death.

Answer 269

Marasmus either protein nor energy, they breakdown their muscle to provide energy for the body, underweight, no fat, lots of muscle loss, old man’s face, no oedema and normal hair. Kwashiorkor: they have sufficient energy, not enough protein, end up with oedema, will not eat (they have enough energy, they don't have any drive to consume any protein), hair pale and thinned, not good skin, moon face (oedema), palpable liver. Other nutrients deficient in PEM Usually: Potassium, magnesium, zinc, vitamin A, iron, folate In some areas: Thiamin & riboflavin (Thailand), Niacin (southern Africa), iodine

Answer 270

GROWTH MONITORING – mother keeps simple weight for height chart and aOends clinic regularly ORAL REHYDRATION – NaCl 3.5g, NaHCO3 2.5g, KCl 1.5g, glucose 20g in clean water to 1L for gastroenteri4s BREAST FEEDING – as long as possible, addi4onal foods not usually needed before 6 months IMMUNIZATION – protec4on against measles, diptheria, pertussis, tetanus, tuberculosis, poliomyeli4s which predispose to PEM and are more serious if child is malnourished Decrease: war, poverty Increase: economic development, safe water/sanita4on, basic health services, women’s status, educa4on, power, baby friendly hospitals, protec4on of nutri4on in crises

Answer 271

• Sources of ammonia – Deamina4on – Inges4on & absorp4on from food (cheese & processed meats) – Genera4on by bacteria in GIT • Urea cycle – Extremely important for removal of ammonia and ammonium ions – Urea formed in a cyclical process on a molecule of ornithine How do we get rid of excess a.a.? how to dispose ammonia? Sources of ammonia come from deamination, ingestion and absorption from food, generation by bacteria in GIT. Urea is formed in a cyclical process on a molecule of ornithine. Carry aroun through the mitochondria and cytosol. Liberated in the form of urea. The concept that there is a number of pt, e.g. glutamate and a.a. transaminated form glutamate.glutamate can then transfer the amino group onto aspartate, that can then contribute to the urea cycle, glutamate can also be delaminated to liberate the ammonia ion then join in the urea cycle, and added onto ornithine to make citrulline and goes around the circle and require ATP. The second ammonia from the transamination picking up the ammonia ion along the way, eventually form urea, the 2 ammonia ion regenerate ornithine, which can then go back to the cycle and pick up more ammonia ions.

Answer 272

• Non-toxic – Can be present in blood at mM levels – Cleared by kidneys • Fish can secrete ammonia – Very dilute! – Ammonia very toxic to us

Answer 273

• Amino group – Fixed nitrogen is quite precious • Recycle if possible – But ammonia is toxic • So need to convert to non-toxic product • Carbon skeleton – Normally a α-keto acid • Oxidized or converted to carbohydrate or fat

Answer 274

• Both in urea cycle and skeleton breakdown • Notably phenylalanine – First step, conversion to tyrosine, some4mes defec4ve – Build up of phenylalanine and phenylpyruvate – Developmental problems – Screening and dietary therapy • Avoid aspartame • Difficult to avoid protein Phe convert to tyrosine can be defective, build up of phe and phenylpyruvate, lead to developmental problem, all baby are screen to this defects. Early prevention can prevent mental retardation. Phenylketourea need to avoid aspartate=artificial sweenter and half of it contain phe.

Answer 275

``` • Very complex! • But all pathways linked to – Glycolysis – Krebs – Pentose Phosphate Pathway • Also other nitrogenous products from amino acids – Crea4ne – Hormones (adrenalin) – nucleo4des ```

Answer 276

we have break down of muscle protein into amino acids, such as glutamate, glutamate can be transaminated to alanine by transfer of amino group and liberate of the alpha-ketoglutarate (this can then go to the creb cycle, to liberate energy which is required for the fasting state). Alanine can then be secreted into the blood, be taken up by the liver, transaminated back into glutamate, it provide pyruvate which can then go to the gluconeogenesis make more glucose for the body, liver is the only one can secreted and buffer BGL, liver is the only organ for gluconeogenesis. Muscle is breaking down, protein into the amino acid, release into the blood, go into liver which liver can make glucose which can then buffer the BGL. then the glucose is used by different tissues such as the muscle. Then the glucose is breaking down by glycolysis to provide pyruvate, which is then available to take that amino group from the glutamate. Cycle continues. Alanine is a common carrier of the amino group ammonia.

Answer 277

Amino acids can be break down into amino group and carbon skeleton. That amino group can be excreted through urea or ammonia, majority is excreted by the kidney, trace amount is excreted by GIT. The carbon skeleton can be used to liberate energy and CO2, the carbon skeleton can go to the gluconeogenesis to generate glucose and/or ketone bodies. Or carbon skeleton can be incorporated into fatty acids.

Answer 278

• Primarily an energy source for our bodies:  􏰶 the preferred fuel for our brains and nervous systems, red blood cells and kidneys  • Structural (within cells)   • Genetic (RNA and DNA)  • Function of certain proteins (glycoproteins)  • Adds taste, texture and colour to our foods and drinks.

Answer 279

* Insulin and glucagon produced by the pancreas - a small tadpole shaped organ that’s behind the stomach. * Itsecretesdigestivejuices and hormones. * Insulin lowers blood glucose. * Glucagon raises blood glucose.

Answer 280

• Adult brains require 140 g of glucose per day • Red blood cells require 40 g of glucose per day • Therefore minimum requirement is 180 g glucose / day • However, gluconeogenesis (lactic acid, amino acids and glycerol) can supply ~130 g glucose per day • So absolute minimum is 50 g glucose per day • However, judgement can be impaired and fetus may be affected in short-medium term • Long-term (≥ 2 years) effects not known

Answer 281

• Very low-carbohydrate ketogenic diet: 20-50 g/d or less than 10% of a 8,400 kJ diet  • Low carbohydrate diet: 230g/d or 45% of energy from a 8,400 kJ diet

Answer 282

* Systematic review and meta-analysis of 19 RCTs comparing low carbohydrate to conventional dietary patterns following 3,209 people for 3-6 months and 1-2 years. * No difference in mean weight loss in the two groups at 3–6 months (MD 0.74 kg, 95%CI -1.49 to 0.01 kg)  * No difference at 1–2 years (MD 0.48 kg, 95%CI -1.44 kg to 0.49 kg)

Answer 283

• Systematic review and meta-analysis of 20 RCTs of 7 different dietary patterns following 3,073 people with diabetes for ≥6 months. • Low-CHO, low-GI, Mediterranean, and high protein diets all effective in 􏰷 HbA1c by 0.12-0.47% points. “Dietary behaviors and choices are often personal, and it is usually more realistic for a dietary modification to be individualized rather than to use a one-size-fits-all approach for each person.”

Answer 284

* Fruit * Vegetables * Milk and yoghurt * Legumes * Grains and pastas * Bread and crispbreads * Breakfast cereals * Savoury snacks * Hot chips/French fries * Soft drinks, juice, ice tea, etc * Confectionery * Table top sweeteners 

Answer 285

Nutrition Information Panels (NIPs) Most commonly total carbohydrate is “‘carbohydrate by difference’, calculated by subtracting from 100, the average quantity expressed as a percentage of water, protein, fat, dietary fibre, ash, alcohol...”5. But it can be “‘available carbohydrate’, calculated by summing the average quantity of total available sugars and starch, and if quantified or added to the food, any available oligosaccharides, glycogen and maltodextrins.”

Answer 286

Carbohydrates are an essential nutrient They include maltodextrins, starches and sugars which all eventually end up as glucose in humans The brain, nervous system and red blood cells are particularly dependant and consequently blood glucose levels are tightly regulated in the body They are found in a large variety of nutritious foods Australians eat a moderate carbohydrate diet Low carbohydrate diets do not improve weight loss or diabetes management in the medium-term (

Answer 287

Where do we find starch? How much do we eat? Characteristics of starch Starch digestion - rate and extent Starch gelatinisation The glycaemic index Resistant starch

Answer 288

Flour, white 73 Rice Bubbles 71 Scone 51 Sweet biscuits 49 Bread, white 45 Bread, wholemeal 40 Crumpet 38 Rice, cooked 28 Cake, plain 30 Pasta, cooked 25 Corn, sweet 17 Potatoes, boiled 13 Sweet potato 8 Baked beans 11 Porridge 9 Bananas 3-7 Pumpkin 3

Answer 289

National Dietary Survey 2011/2 Males 136 g per day (24% E) Females 103 g per day (24% E) Decreased by ~18% compared with 1995 survey Eating more discretionary foods (~1/3rd of daily energy)

Answer 290

Plant energy reserve Storage organs: seeds (cereals and legumes), tubers, unripe fruit (esp. banana) Starch granules Unique in shape and size to each plant Rice starch: small and angular Potato starch: large and more spherical

Answer 291

amylose - linear molecule | amylopectin – branched molecule

Answer 292

Most plants contain starch ratio of 80% amylopectin / 20% amylose More amylose (ie 30-60% of starch) in: Legumes, Basmati rice, Hi-MaizeTM starch Amylose tends to line up in rows Amylose gelatinises at a higher temp. Amylose is digested more slowly

Answer 293

Starch granules swell in presence of water and heat = gelatinisation Causes thickening If starch conc’n is high, a gel will form Gravies, soups, custards, desserts Temp of gelatinisation depends on; sizeofgranule,amylosecontent

Answer 294

Depends on: rate of stomach emptying rate Fat and protein slow it down susceptibility of starch to α-amylase Degree of gelatinisation Amylose content Physical entrapment in fibrous cell walls viscosity of luminal contents More viscous means slower

Answer 295

``` Treatment of diabetes hyperglycaemia and hypoglycaemia Prevention of type 2 diabetes Prevention of coronary heart disease Satiety, appetite control, weight reduction Sporting performance ```

Answer 296

A tool to rate the glycemic potential of the carbohydrates in different foods (as eaten)

Answer 297

Compares foods gram-for-gram of carbohydrate Compares the ‘area under curve’ over 2 hours Relative to a reference food 50 g glucose load GI = 100 Published GI = 10 subjects 640 datapoints in total

Answer 298

Feed 50 g CHO portion of the food to 10 subjects eg 200g spaghetti Measure blood sugar at regular intervals 0, 15, 30, 45, 60, 90 and 120 mins Calculate ‘area under the curve’ Compare with area after reference food Reference food is tested on three separate occasions express as % Calculate the average (%) for all 10 individuals

Answer 299

Originally considered that cooked starch was completely digested in the small intestine But certain starch fractions can pass through the small intestine intact Some of it undergoes microbial fermentation in the large intestine Resistant starch = starch that escapes digestion in the small intestine ~3-10% of total starch in many foods is resistant starch

Answer 300

Metabolic effects Improved glucose tolerance? Lowering of blood lipids? Blood pressure lowering?? Gastrointestinal effects Colonic fermentation Lower pH in colon hhFree fatty acids Increased faecal bulk hh Bifidobacteria iiRisk of colon cancer?

Answer 301

Digested at different rates in different foods Some of it completely resistant to digestion Modern starchy foods have a high GI The GI has important implications for health Resistant starch is quantitatively as important as fibre Need to reduce the rate and extent of starch digestion

Answer 302

Naturally-occurring + ‘added’or refined sugars Analytically impossible to tell apart Both groups include: • Glucose • Fructose • Sucrose (split to glucose and fructose during digestion) Lactose • the sugar in milk and dairy products • split to glucose and galactose during digestion

Answer 303

Sucrose from sugar cane Sucrose from sugar beet Corn syrups (from corn/maize) a mixture of short chain glucose polymers High fructose corn syrups (USA) fructose:glucose ratio is 55:45 Honey is treated as a refined sugar in food records

Answer 304

According to food records Males 50 - 70 g/day Females 35 - 50 g/day Children 40 - 50 g/day ~10% of total energy intake Most experts consider 10% E acceptable

Answer 305

* Using NNS 1995 data, the total sugar content was apportioned as either added or natural by dietitians * Men consumed 10.4% of kJs from added sugars * Women consumed 9.4% of kJs from added sugars • Adults ~9.9% of kJs from added sugars * Equivalent to 59.5 g of added sugars per day, or 12 teaspoons * If consumption patterns the same in 2011/2, then ~9.8% of kJs from added sugars, equal to 53 g of added sugars per day, or 10.5 teaspoons

Answer 306

Added sugars are ‘empty’ calories/kilojoules Added sugars cause micronutrient deficiencies Added sugars stimulate appetite Added sugars make you fat Cutting added sugars will cause weight loss Reducing added sugars will prevent tooth decay

Answer 307

“Intakes at various times during history may well have rivalled our current consumption of refined sugar”

Answer 308

apple: 218kj/100g orange juice 188kj/100g coke 157kj/100g

Answer 309

``` Beer Wine and spirits Refined starches Maltodextrins Gluten Mostly empty calories... White rice (50%E) Crispbreads Low fat, low sugar snacks Cakes and biscuits Refined oils ```

Answer 310

several dietary metrics that are currently emphasized, such as fat content, energy density, and added sugars, would NOT have reliably identified the dietary factors that we found to be associated with long term weight gain

Answer 311

Randomised controlled trials are | the “gold standard”

Answer 312

• 20+ systematic literature reviews published to-date • Some include observational studies and randomised controlled trials • Others include only randomised controlled trials • The SLRs that include both generally conclude that SSBs contribute to weight gain • The SLRs that only include RCTs generally find more equivocal results

Answer 313

- saturated fat, high GI starches, salt and alcohol

Answer 314

Sugars come from both naturally-occurring and ‘added’ sources Sugars have been important energy source throughout human evolution Australians have reduced intake of added sugars ~10% E. Americans eat 16% E as added sugars The role of added sugars and sugar-sweetened beverages in obesity requires more research

Answer 315

• No general agreement • Any substance of plant origin which is undigested by human alimentary enzymes’ (Trowell, 1972) • Plant polysaccharides + lignin* which are resistant to hydrolysis by the digestive enzymes of man (Jenkins, 1988) • British report avoids term‘dietary fibre’ • Uses ‘non-starch polysaccharide’ (NSP) instead

Answer 316

• • Cellulose is a polymer of glucose • (β-1,4glycosidicbonds) • • β-glucans are shorter, viscous glucose polymers • (β 1-3 & β 1-4 glycosidic links) • • Hemicelluloses are mixed polymers of glucose, galactose, xylose, mannose,arabinose • • Pectins are polymers of galacturonic acid Gums Highly viscous plant exudates Highly complex structures Algal polysaccharides Eg alginates, carrageenan Lignin is a polyphenolic compound the‘woody’, gritty fraction of strawberries and pears

Answer 317

Wholegrains (the bran layer only) Fruit Vegetables Total intake in Australia 27 g/day for men 21 g/day for women Recommended level 30 g/day A rich source of fibre provides 3 g 1 serve All-BranTM provides ~10 g

Answer 318

``` A complex procedure Not yet standardised Two main approaches: The‘chemical’ eg Englyst method The‘gravimetric’ eg Prosky method Prosky’s method is simpler, cheaper But it includes some resistant starch and gives higher values ```

Answer 319

soluble in water, maybe viscous

Answer 320

insoluble in water, particulate

Answer 321

Dissolves in water May become viscous Pectins, gums, β- glucans, psyllium Apples, legumes, oats are rich in soluble fibre

Answer 322

Remains as particle Never viscous Cellulose, lignin Wheat bran is high in insoluble fibre

Answer 323

``` Soluble fibre Increases luminal viscosity Slows passage through small bowel Reduces blood glucose Reduces blood cholesterol Fermented in large bowel ```

Answer 324

``` Insoluble fibre Accelerates movement through small bowel No effect on glucose No effect on cholesterol Not fermented but absorbs water Increases faecal bulk ```

Answer 325

Undigested CHOs are fermented by bacteria Short chain fatty acids produced and absorbed Acetic Propionic Butyric Typical ratio 60 : 24 : 16 Perhaps some lactate Gases produced (flatus): CO2, H2, CH 4

Answer 326

``` - Short chain fatty acids >70% absorbed Utilised for energy Lactic acid is not absorbed Reduces faecal pH Inhibits pathogens Probiotics? - Gases Some expelled as flatus Some expired in breath Breath hydrogen test assesses carbohydrate malabsorption ```

Answer 327

Energy source for colonic epithelial cells Cell growth regulator Controls differentiation Important to large bowel health May reduce risk of polyps and colon cancer

Answer 328

Increases stool water (dilution) Reduces residence time in large bowel Increases the binding of carcinogens Reduces colonic pH Produces more desirable bowel flora Increases butyrate production

Answer 329

Higher intakes of fibre increase insulin sensitivity Reduced insulin levels (fasting and postprandial) Reduced risk of cancers of all kinds Reduced risk of Type 2 diabetes, CVD and stroke Cereal fibre more strongly than fruit and veg May be confounded by ‘healthy’ lifestyle behaviours

Answer 330

Physical discomfort loose stools Flatulence ‘rumblings’ Need to increase fibre gradually Phytate in bran binds Zn and other minerals May be associated with Zn deficiency Phytate is not fibre but usually accompanies it

Answer 331

Fibre comes in different chemical forms There is more insoluble fibre than soluble fibre Soluble and insoluble fibres have differing physiological effects High fibre intakes may be important for bowel health via multiple mechanisms High fibre diets are associated with reduced risk of chronic disease

Answer 332

• Compounds that dissolve in organic solvents (e.g. chloroform) – Oils, liquid at room temperature – Fats, solid at room temperature • Most lipids can be synthesised by humans – Contribute to structure and function of cells – Source of energy (37 kJ/g; 9 kcal/g) • Some lipids not synthesised by humans, but are required for proper structure/function – Essential fatty acids

Answer 333

• Most dietary fat is comprised of triglycerides, phospholipids, and sterols • Dietary fat contributes on average 25-40% of energy intake – Animal and plant sources – Source of energy (37 kJ/g; 9 kcal/g) • Other macronutrients?

Answer 334

Triglyceridesmakeup>90%oftotaldietarylipids – Glycerol backbone + 3 fatty acids • Fattyacids – Variable degree of saturation (with hydrogen) – “Saturated”, “Monounsaturated” and “Polyunsaturated” – 3 main series of unsaturated fatty acids: position of first double bond counting from methyl carbon (“omega” or “n”) • Omega-9 or n-9 • Omega-6 or n-6 • Omega-3 or n-3

Answer 335

› Some polyunsaturated fats (oils) are “hydrogenated” by the addition of a hydrogen across a double bond - Conversion of isomers from cis to trans configuration - Change in physical behaviour of fatty acid: trans fats are solid at room temperature - Relevance for industrial food production? › A small amount of naturally occurring trans fatty acids in milk and dairy products - Different physiological effects to industrial trans fats?

Answer 336

› Types: phosphatidylserine, phosphatidylcholine... › Function: emulsifier, component of cell membranes (lipid bilayers) › Sources: egg yolks, liver, wheat germ, peanuts, most oils

Answer 337

• In animal tissue cholesterol is the principal sterol • Often has a fatty acid esterified to it • In plants the main sterols are sitosterol, campesterol and stigmasterol (phytosterols)

Answer 338

• Key points – triglycerides mixed with amphipathic compounds such as bile acids and phospholipids for emulsification – Pancreatic lipase acts on emulsified particle to hydrolyse triglycerides - removing 2 fatty acids • Importance of emulsification – Phopholipase – Cholesteryl ester hydrolase – Hydrolysed lipids diffuse into the mucosal cells of the small intestine

Answer 339

• Lipids are insoluble in plasma - an aqueous environment. • In order to be transported they are combined with specific proteins to form lipid-protein complexes called lipoproteins • 2 pathways: – Exogenous pathway: lipoproteins are formed in intestinal cells after lipids are absorbed – Endogenous pathway: lipoproteins are formed mainly in the liver for transport to tissues

Answer 340

› Hydrophilic membranes - Protein: apolipoproteins - Cholesterols and phospholipids › Triglyceride and cholesterol ester rich core

Answer 341

Intestine. | Transport and delivery of dietary fat (mainly TAG).

Answer 342

Liver. | Transport of endogenously synthesised lipids (cholesterol and TAG).

Answer 343

Product of VLDL; peripheral tissues / capillaries. | Delivers cholesterol and triglycerides to peripheral tissues.

Answer 344

Product of IDL. | Delivers cholesterol and triglycerides to peripheral tissues.

Answer 345

Liver. | Removes cholesterol from tissues and takes it to liver.

Answer 346

› Total cholesterol › LDL cholesterol › HDL cholesterol › Triglycerides › Not the same as the lipoprotein classes - Don’t reflect the number of particles or the amount of protein › Perceptions of good vs bad, based on association with disease - Relevant? Maybe - Nuanced? No › Fasting vs non-Fasting - Why? › Direct vs calculation - Friedewald equation (Clin Chem 1972) - LDL-c = TC - HDL-c - (TG/2.2) - Restrictions 1. Chylomicrons present 2. People with type III hyperlipoproteinemia 3. Triglycerides >4.5 mmol/L

Answer 347

* positively associated with atherosclerosis * Non-linear * desirable range:

Answer 348

HMG-CoA reductase - Targetof“statins” - HMG-CoAreductaseinhibitors

Answer 349

* negativelyassociated with atherosclerosis * usuallyhigherin women than men * desirablerange * Men: >1.03 mmol/L * Women: > 1.30 mmol/L * regulatedbydiet(eg. alcohol), physical activity, and genetic factors

Answer 350

› Results of Mendelian randomization studies - Contrasting results for HDL-c and LDL-c › Three large trials of HDL raising agents and CVD stopped early - increased rate of CVD - Futility / lack of efficacy - Torcetrapib, Dalcetrapib, Niacin › Not a causal association between HDL-c and CVD › Potential as a risk marker?

Answer 351

› Triglycerides are lowered by: - Niacin - Omega-3 fatty acid (high dose) - Fibrates 10-50% reduction 20-50% reduction 30-50% reduction - These interventions don’t seem to reduce risk of coronary heart disease › AHA scientific statements: “triglyceride is not directly atherogenic but represents an important biomarker of CVD risk”

Answer 352

› Saturated fat is the main dietary factor that determines LDL-c levels › Mechanisms: - downregulation of LDL receptors › C12 - 16 are cholesterol raising - LDL and HDL are increased › C18 (stearic) – may lower LDL-c

Answer 353

cis MUFA & PUFA › PUFA (n-6) & MUFA decrease LDL-c (relative to SFA) › Mechanisms: - Increase in endogenous cholesterol synthesis - upregulation of LDL receptors & redistribution between plasma and tissue

Answer 354

› Dietary cholesterol increases LDL-c levels (although not to same extent as SFA) › Co-inhabits with SFA › Trans fats increase LDL-c (relative to SFA) › Mechanisms - Increase in endogenous cholesterol synthesis

Answer 355

› Sterols of plant origin - Reduce blood cholesterol (incl. LDL cholesterol) by up to 10% at highest dose - Australian regulations - margarine spreads, breakfast cereal, low-fat yoghurt and low-fat milk - Mechanism? Compete with cholesterol for absorption in the gut

Answer 356

› RCTs - Surrogate endpoints (lipids and other CV risk factors; progression of atherosclerosis) - Cardiovascular events (BIG trial, aka expensive) - Dietary vs supplementation (eg. fish vs fish oil) - Difficulties with compliance › Cohort - Cardiovascular events and mortality - Difficulties in accurate assessment of dietary intake - Small snapshot of lifetime intake - multiple 24h recalls, diet diary, FFQ - Difficulties in analysis of individual nutrients - Accounting for dietary energy

Answer 357

› Total dietary energy intake may be a primary determinant of disease › Absolute intake of most nutrients is positively correlated with total energy intake › In the absence of change in weight or change in physical activity, long-term total energy intake remains stable. - Average adult gains ~500 grams per year (about 1 potato crisp per day) - As such, dietary recommendations should be made in reference to total energy intake (eg. fat as % energy) › Nutritional epidemiology: it is important to adjust for total energy intake - (at least partially) accounts for differences in absolute intake due to measurement error - Analogous to iso-caloric experiment

Answer 358

› Dependent on “background” dietary intake - For example, carbohydrates... - Poor quality --- high GI, refined carbohydrates - Problematic when comparing between different populations - Geographic: cultural and regional - Chronological: population shift in background dietary intake › What other study types should we consider? › Substitution of energy from SFA for energy from ???

Answer 359

› Theoretical increase in inflammation with omega-6 PUFA intake - Potentially compete with the anti-inflammatory effect of omega-3 PUFA - Little direct evidence in humans to support › How best to study in RCT... - Increase omega-6 PUFA (↑ ratio) - Decrease omega-3 PUFA (↑ ratio) - Is effect due to the ratio or individual absolute amounts n-3 or n-6 PUFA? - Keep % energy from PUFA constant? - If not, is effect due to inherent replacement of PUFA for other macronutrient? THERE IS NO RIGHT WAY!

Answer 360

› Randomized crossover trial in dyslipidemic patients on statins › Isoenergetic diets that differed by omega-6:omega-3 ratio › Both had 8% energy from PUFA - Low ratio (goal 1.7:1; actual 1.2:1) - omega-6 ~9 g/day; omega-3 ~8 g/day - High ratio (goal 30:1; actual 37:1) - omega-6 ~17 g/day; omega-3 ~ 0.5 g/day Low ratio: LDL-c 3.0 mmol/L → 2.3 mmol/L; P = 0.02 High ratio: LDL-c 3.0 mmol/L → 2.3 mmol/L; P = 0.06

Answer 361

Real world vs macronutrient intakes: use of dietary patterns and whole foods as opposed to individual nutrients › Mediterranean diet › Vegan / vegetarian › Dairy › Fish vs red meat › Nuts › Fruit & veg

Answer 362

Similar in USDA recommendations 2010 & NHMRC guidelines 2013 › Overall healthy eating pattern: Include a variety of fruits, vegetables, grains, low-fat or nonfat dairy products, fish, legumes, poultry, lean meats. › Appropriate body weight: Match energy intake to energy needs, with appropriate changes to achieve weight loss when indicated. › Desirable cholesterol profile: Limit foods high in saturated fat and cholesterol; and substitute unsaturated fat from vegetables, fish, legumes, nuts. › For people without CVD: Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in alpha-linolenic acid (flaxseed, canola, and soybean oils; flaxseed and walnuts) › For people with CVD: Consume ≈1 g of EPA+DHA per day, preferably from oily fish.

Answer 363

› An organic factor distinct from carbohydrate, protein or fat › Water-soluble (9) OR fat-soluble (4) › A natural component of food – usually in very small amounts › Has an ESSENTIAL biochemical role in the body › Causes, by its absence a distinct deficiency › Not made in the body › Required in ‘small, ‘very small’, ‘tiny’ or ‘minute’ amounts: a micronutrient

Answer 364

Ascorbic acid C B COMPLEX - Thiamin B1 - Riboflavin B2 - Niacin B3 - Pantothenic acid B5 - Pyridoxine B6 - Biotin B7 - Folate B9 - Cobalamin B12

Answer 365

› Circulate freely in blood, interstitial fluid and cytosol (except B12 which is transported) › Excess excreted by kidneys (except folate & B12 - regulated by liver and converted to bile) › Limited stores in body › Regular intake required (except B12)

Answer 366

› Regular intake required (except B12) › Lost in cooking and processing - Water leaching - Some heat sensitive - Depleted in refined grains › Generally non toxic › B vitamins – active form is a coenzyme

Answer 367

› Vitamin A › Vitamin D › Vitamin E › Vitamin K › Bile required for absorption of vitamin into lymph system from intestines › Stored and used in liver and fatty tissues

Answer 368

A couple of definitions › RDI – recommended dietary intake: The average daily dietary intake level sufficient to meet the nutrient requirements of 97-98% of health individuals at a particular life stage / gender › EAR – estimated average requirement: The estimated daily amount of a nutrient required to meet the requirements of half the healthy individuals at a particular life stage / gender › AI – adequate intake: The average daily nutrient intake level based on observed or experimentally-determined approximations or estimates of nutrient intake by a group (or groups) of apparently health people that are assumed to be healthy › UL – upper limit: the highest average daily nutrient intake level likely to pose no adverse health effects in almost all individuals in the general population.

Answer 369

› Primary extra-cellular cation – important in regulation of blood volume › Important also in nerve impulse transmission, muscle contraction and acid- base balance (excretion of H+ ions in exchange for Na+) › Rarely a limiting factor in the diet › Excess intake, under normal conditions excreted by kidneys to keep [Na+] tightly regulated. Thirst response triggered, firstly diluting Na, then excreting Na+ and H2O together

Answer 370

› High NaCl intake (not simply high Na+ intake) associated with hypertension - Some people more salt sensitive than others and BP may increase in direct response to salt intake - Risk factors: family history, age over 50 years, chronic kidney disease, T2 diabetes › High NaCl associated with increased Ca mobilisation/excretion and risks of osteoporosis › Na restricted diet has BP lowering effects in both hypertensive and normotensive individuals

Answer 371

› In general, the more processed a food, the more likely it will contain added NaCl - ~75% of salt intake in most diets comes from processed foods. - Note: salt is used as a preservative in some foods and will also mask bitter tastes. - Foods such as corned / preserved meats, aged pickled foods, foods in ‘brine’ all have added salt. - Cheeses, esp harder and more processed cheeses are also high in salt. - Bread has higher salt than the national guidelines state. Bread is a staple in the diet and the higher allowed levels are more about palatability

Answer 372

- is an evidence based dietary approach shown to lower BP - There are variations on this, but essentially it is based on the core food groups, with an emphasis on fruits, vegetables, low-fat dairy, wholegrains, nuts and lean protein (with lower intakes of red meat and saturated fat foods). - Lower in Na but rich in K

Answer 373

› Men and women: AI 460-920mg/d › Men and women: UL 2300mg/d › 1 in 3 Australian adults consume more than UL on a daily average

Answer 374

› Primary intra-cellular cation › Major roles: fluid balance, cell integrity, nerve conduction › Abundant in all living cells: therefore unprocessed foods are good sources › Absorbed in ileum › Review biochem notes Y2

Answer 375

``` In descending order: › Cocoa powder › Vegemite › Dried apricots › Unprocessed wheat bran › Potato chips › Pistachio nuts › Wheat germ › Dark chocolate › Rich, uniced fruit cake › Grilled beef › Canned baked beans › Dairy (milk and yoghurt) ```

Answer 376

› Steaming / microwaving of vegetables retains significantly more potassium than boiling as less leaching into water. › Some losses (often with attendant addition of Na) in processing, even with minimal processing such as canning. Further losses with greater processing, especially where cells are broken open eg breakfast cereals, processed meats

Answer 377

› Low K+ intake: - associated with hypertension, kidney stones, increased bone turnover - see notes on refeeding syndrome - chronic low K intake can result in irregular heartbeat, muscle weakness, glucose intolerance, irrespective of refeeding status › Inadequacy may result from - inadequate dietary intake, or dehydration - drug use eg diuretics, laxative abuse, - excessive vomiting (all causes, including bulimia) - Certain disease states eg kidney disease, diabetic acidosis › Alcoholics, those with ED are at risk of deficiency

Answer 378

› High intakes, esp in conjunction with low Na+ associated with reduced BP › (Adrogue, HJ, Madias, NE ‘Sodium and potassium in the pathogenesis of hypertension’ New England Journal of Medicine, 2007; 356: 1966-78) › AI: Men – 3800mg; Women – 2800mg

Answer 379

› found as PO43- and in elemental form

Answer 380

› Roles: - 80-85% found with Ca in inorganic portion of bones and teeth - Essential component of every cell and metabolites – incl. DNA, RNA - Integral to phospholipids - Important role in energy conversion and transfer as ATP - Important in regulation of pH › Approximately 60% absorption › RDI: - M/F: 1000mg/d

Answer 381

› Rare if protein and calcium intake adequate. At risk includes: - Near starvation - see refeeding syndrome notes - Alcoholics - Diabetics post ketoacidosis - Renal disease when on phosphate binders or antacids - Long term TPN - Anorexia nervosa

Answer 382

› Potential signs/symptoms of deficiency: - Muscular weakness - Bone pain - Loss of appetite - Rickets in children - Difficulty walking - Tingling in extremities

Answer 383

``` › Extruded rice bran › Unprocessed wheat bran › Sunflower seeds › Unprocessed rice bran › Raw cashews › Almonds (skin on) › Peanut butter › Meat, poultry, fish (variable) › Firm tofu › Whole eggs › Regular milk › Pure (35% fat) cream ```

Answer 384

› Adults - ~100mg Cu total › ~10% in blood, associated with caeruloplasmin - ferridoxidase activity (Fe2+àFe3+) › Found in skin, muscle, liver, brain › Acts as part of metalloenzymes. Some functions include: - erythropoiesis - connective tissue synthesis (lysyl oxidase) - oxidative phosphorylation - thermogenesis - cardiac function - ALL Cu-containing enzymes involve reactions consuming oxygen or oxygen radicals

Answer 385

› Absorption - Active saturable transport - Passive absorption - Upper GIT absorption – stomach and duodenum - Inhibited by 10x increase in molar ratio with Zn and Fe - Enhanced by histidine › Excretion - Faeces (unabsorbed and endogenous excretion) - Urine

Answer 386

› Intake: no RDI (US 2mg) - No national data - Widely distributed in food (esp legumes and shellfish) - Variable intake (variable quantities in water – Cu pipes) › Sources: lecumes, wholegrains, nuts shellfish and seeds › Toxicity - GI discomfort – nausea and vomiting - Hepatic necrosis - Haemolytic anaemia › AI: men: 1.7mg/d; women 1/2mg/d › UL: 10mg/d

Answer 387

› Deficiency - Rare - Symptoms: anaemia, connective tissue eneurysms, decreased skin tone, hypothermia - Mild deficiency can be cause by excess Zn intake - Inborn error of metabolism – - Menke’s disease (intestinal cells absorb Cu but cannot release it to circulation) - Wilson’s disease – Cu accumulates in liver and brain, creating life-threatening toxicity – controlled by reducing Cu intake, using chelating agents and taking Zn supplements which interfere with Zn absorption

Answer 388

``` › Group II metal, element 20, MW=40 › ~1.0kg in the whole body Ca store › Common anions: - Gluconate - Lactate - Carbonate › Distribution - Skeleton – 99% of body Ca - Teeth – 0.6% - Plasma – 0.03%, and of that - 46% is protein bound - 7% low MW complexed - 47% ionised ```

Answer 389

1. Structural - Provides framework for vertebral body – skeleton and teeth 2. Metabolic activity - Membrane permeability - Nerve conduction - Muscle contraction - Blood clotting cascade, in eg interactions with Vit K - Enzyme regulation - Second messenger – intracellular signaling – Ca regulates enzyme action by phosphorylation / de-phosphorylation

Answer 390

Calcium is in constant exchange between - Skeleton - Intestine - Kidney Aim to keep plasma calcium within a narrow range Mediated by: - Parathyroid hormone (PTH) - Calciotropic hormones - 1,25-dihydroxycholecalciferol - calcitonin

Answer 391

``` › Growth › Pregnancy › Lactation › Age › Menopausal status for women ```

Answer 392

``` › two mechanisms - active, saturable, transcellular process regulated by vitamin D - passive, non-saturable, paracellular › upper GIT (ileum) › Limited absorption in the colon › Increased during pregnancy › Ageing reduces absorption and increases excretion › influenced by - stomach acidity - digestion - interactions with a range of anions ```

Answer 393

› Dietary protein - High intakes related to high Calcium losses - Low intake (

Answer 394

› Increasing dietary fibre (bread) results in a decrease in Ca retention in elderly subjects › Ca was 245-275 mg › Phytate increased from 0.035g to 0.35g

Answer 395

› uronic acid is a constituent of dietary fibre which binds calcium › intake of uronic acid ~ 2-3g/d, mostly from soluble fibre sources

Answer 396

=cholecalciferol natural form, different form used in supplements important for bone health and maintaining the immune system function. may also have a preventative role in cancer.

Answer 397

* phytosterol * p harmaceutical * f ortification of foods eg. margarine

Answer 398

naturally occurring form of vitamin D in humans and animals

Answer 399

› Regulation of calcium metabolism - when plasma [Ca] falls, parathyroid hormone (PTH) is secreted - PTH stimulates production of 1,25(OH)2D - 1,25(OH)2D increases blood calcium levels ->Ca absorption is increased Ca excretion is decreased Ca is mobilised from bone AND more than 2000 genes are regulated by vitamin D

Answer 400

› Enhances intestinal absorption of Ca › PTH exerts its effect on intestinal calcium absorption via the Vitamin D metabolite 1,25(OH)2D (calcitriol, D3) › Facilitates Calcium absorption in the kidney › Important for bone calcification and mineralisation › Vitamin D also involved in the resorption (release) of Ca from bones

Answer 401

› No RDI › AI: M/F - 19-50: 5μg M/F - 51-70 : 10μg M/F - >70: 15μg

Answer 402

``` Limited › Small quantities are found in: - Fatty fish: salmon, herring, mackerel - Liver - Eggs - Fortified foods, eg - Milk - Orange juice - Breakfast cereal ```

Answer 403

› Reduced calcification of bones: - Rickets when bones are still growing - Occurs at site of growth plate = soft bones and difficulty / unable to weight bear - Osteomalacia when deficiency in mature bones

Answer 404

Risk factors for Rickets5,6 › 1st and 2nd century: ‘disease of lack of nurture and hygiene’ › 19th and early 20th century: ‘disease of poverty and darkness’ › Vitamin D deficiency - Particularly low sun exposure - More common in northern hemisphere (decreased UV exposure in colder climate) - More common in dark skinned people › Severe bone deformities are now rare

Answer 405

› Result of vitamin D deficiency in adults › Decreased mineralisation of newly formed bone matrix › Results in muscle weakness › Osteoporosis (OP) often accompanies Osteomalacia › Most common symptom is pain and muscle weakness - Deformities are rarely seen › Risk factors are the same as for rickets, though it is associated with malabsorption or genetic disorders

Answer 406

``` › Kidney - Body’s main site of excretion - Excretion highly regulated - Ca and Na excreted simultaneously - Na ingestion promotes Ca excretion › Endogenous excretion - Excretion through bile into the intestine - Available for re-absorption › Faecal excretion - Highly variable amounts excreted › Sweat - Small losses through perspiration ```

Answer 407

``` › Decrease: - Intake of soy foods (phytoestrogens) › Increase: - Na (obligatory co-excretion of Ca) - protein - 150 mg Ca is excreted/50 g dietary protein - caffeine ```

Answer 408

› Bone loss - Bone Ca is mobilised to maintain muscle function - New bone formation is hindered › Reduced growth rate - Affects growing children › Tetany - muscle neurological disorder

Answer 409

› Oestrogen and testosterone support bone formation › Loss of oestrogen = increase in bone remodeling, especially bone loss › 5-10yr post menopause - Bone loss more rapid than men (2-3% per year) - Evidence shows high Ca intake can slow this - Thereafter: age related loss is 0.5 – 1% per year for men and women › Losses are due to decreased intestinal absorption +/- increased urinary Ca excretion › Hypogonadism in young males results in decreased testosterone and low bone density = increased risk of OP › History of parental fracture increases risk of fracture › Confounders: often reduced weight bearing exercise

Answer 410

Smoking increases risk of hip fractures up to 1.5 fold › Risk from smoking starts early and increases with age › Swedish studies show young males (18-20yr) have reduced BMD and thinning of the cortical bone › Post menopausal smokers have a much more rapid decline in BMD Over 4 standard drinks per day can double risk of hip fracture › Excessive alcohol decreases BMD - ?toxic effect on osteoblasts › Likely influence also of increased falls risk and poor nutrition in alcohol abusers

Answer 411

› Include diseases that affect bone remodeling and mobility (covered in previous lectures) › Certain medications - Long term glucocorticosteroids and immunosuppressants - Used in COPD, Rheumatoid Arthritis, Crohn’s Disease - Certain antipsychotics and anti-epileptics - Methotrexate - Antacids and proton pump inhibitors

Answer 412

“eat foods containing calcium. This is particularly important for girls and women“ › Aims are to - increasethecalciuminbones - increasebonedensity, - reducefractures

Answer 413

Revised Australian Guide to Healthy Eating20 › Requirements dependent on age/gender - ~2.5 - 4 serves per day › 1 serve = - 250ml fresh milk - 125ml evaporated unsweetened milk - 200g (3/4 c) yoghurt - 40g hard cheese (e.g cheddar) - 120g ricotta

Answer 414

› Peak bone mass attained in mid-20’s › Need adequate Ca intake to ensure high bone density for remainder of life › Also require regular menstrual cycle to maximise bone health › Low peak bone mass = ↑ fracture risk › Need adequate energy, protein, Ca and nutrition in general for healthy growth & bone development

Answer 415

› Amennorhoea - Late menarche or menstruation stopped or irregular › Osteopaenia - Low bone density, risk of fracture › Body fat - Restricted eating patterns, eating disorders - Very low body fat levels - Impacts oestrogen metabolismðimpacts bone

Answer 416

› OP develops in 35-50% of those with Anorexia Nervosa › Decreased calcium intake → mineral loss from bone > deposition › Extreme weight loss → stop producing hormones › Oestrogen deficiency speeds up bone loss in a similar way to post menopause › Poor bone quality in early life → poor investment in bone bank

Answer 417

``` › Some causes - Hyperparathyroidism - Vitamin D toxicity - renal failure › Symptoms - Muscle weakness, fatigue - Nausea, vomiting - Cardiac arrythmias ```

Answer 418

› Total body content: ~25g (~1.04mol) – 2nd most common cation - 60% in skeleton – ~1/3 of this on the surface of bone as part of the hydroxyapatite mineral component - Moderately available exchangeable pool to maintain serum/soft tissue [ ] in depletion (% bone Mg available in this form declines with age) - 30% in muscle - 2-8% in other cells - 1.2% in ECF - 35% total is protein bound › Homeostasis maintained by efficiency of - intestinal absorption - renal losses (stronger mechanism) – active reabsorption in distal convoluted tubule of loop of Henle

Answer 419

› Found as: - ionized (Mg2+) - bound to nucleotides & small organics (e.g, MgATP2-) - bound to proteins › Essential for all PO43- transferring systems - Phospho-transferases and hydrolases - β-oxidation, nucleic acid synthesis, protein synthesis - ATP and ADP exist in cells as Mg salts

Answer 420

› Phosphate-transfer reactions › Nucleic acid synthesis and storage (Mg salts) › Protein synthesis › Carbohydrate metabolism › Hydrolysis reactions (fatty acid oxidation) › Ion channel permeability

Answer 421

› Mg2+ binds phosphate groups | › Enzyme substrate binding sites: promotes interaction

Answer 422

1. Absorption - SI - 20-70% bioavailability from a meal (gen 40-60%) - 50-90% of maternal milk / formula available for infants 2. Mechanism of absorption - Saturable active transportàlikely the regulatory mechanism - Simple diffusion (paracellular) - Solvent drag (ie following H2O)

Answer 423

1. › Enhancers - Vitamin D, lactose 2.› Inhibitors - Weak interference - Phytate / fibre - Excessive unabsorbed fats - High doses Ca2+ / PO43- 3. › Excretion - Faecal and urinary losses - Endogenous excretion ~30mg (10% intake) per day - Influenced by urinary [Na] and acid-base balance –é urinary pHàêurinary Mg output (even with increased dietary Mg) - Dietary Ca in XS 2600mg/d, esp ass’d with hi Na intake à increased urinary output

Answer 424

› Serum: 0.7-1.0 mM - Most commonly used - plasma not suitable – anticoagulants may be contaminated with Mg › Urinary excretion (24 h): 75-150 mg (i.e. 3-6 mmol) › Magnesium load test - IV infusion (30 mmol over 8 h) then measure 24 h urine excretion • If > 80% excreted - normal • If

Answer 425

› Animals: - Growth retardation - Neuromuscular symptoms - Excessive muscle twitching - Hyperexcitability - Convulsions › Humans - Highly uncommon in those who are well with varied diet due to abundance of Mg in food supply - Experimental deficiency - Weakness, anorexia - Varied biochemical abnormalities (refer refeeding notes)

Answer 426

› Deficiency - Cessation of bone growth - Decreased osteoblast and osteoclast activity - Osteopenia (decreased BMD) - Increased bone fragility › Positive association between Mg and bone mass / markers of bone metabolism

Answer 427

› Dietary | - Habitual, sustained low Mg2+ intake (

Answer 428

› SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) – various causes › Increased requirements eg pregnancy, lactation › Endocrine disorders eg - parathyroid disoders - Hyperaldosteronism:primaryandsecondary › Hungry bone syndrome (may occur after parathyroidectomy) › After major burn › After gastric bypass surgery

Answer 429

When it does occur... › Anorexia, nausea, vomiting › Agitation, Depression, Psychosis, Seizures › Hypokalemia concurrent › Hypocalcaemia concurrent (NB Mg required for PTH secretion) › Serum Na generally remains unchanged › Cardiac Arrhythmias › Tremor, Fasciculations (small local muscle twitch), Spasm/tetany

Answer 430

Hypertension - High Mg foods associated with lower blood pressure - Mg infusions for treatment of malignant hypertension e.g., pre-eclampsia › Heart disease - Communities with ‘hard water’: lower rates of heart disease › Diabetes - May promote insulin secretion and sensitivity in Type 2 DM › Migraines - Sufferers have lower intracellular levels - Supplements may reduce frequency of attacks › BMD - Supplements have been shown to increase hip BMD in per-adolescent girls with habitual low Mg intake

Answer 431

``` National Nutrition Survey (1995) › Intake for men 381 mg/day; women 283 mg/day Contributions from food groups - Cereals and related 32% - Fruit and vegetables 18% - Milk and dairy 12% - Meat and meat products 10% ```

Answer 432

Humans - Hypotension - Laxative effect of single large doses of Mg Animals - Paralytic effect - Loss of reflex - Cardiac arrest

Answer 433

Caffeine: › Increases urinary Ca excretion › Very small decrease in intestinal Ca absorption › Associated with bone loss in women › Studies show that Ca intake

Answer 434

› Soft drink consumption has increased significantly - Often displacing milk or water in diet › Most cola drinks contain caffeine › Framingham Osteoporosis Study: intake of cola, but not of other carbonated soft drinks is associated with low BMD in women - Large population based cohort (women n =1413, men n =1125) - Cola intake assoc'd with significantly lower BMD at hip site in women (but not in men) - Similar results found for diet cola, but not decaffeinated cola - More research needed to confirm these findings - Role of phosphoric acid is controversial - ? The role of displacing milk from the diet

Answer 435

Increase bone density and prevent bone loss › Regular weight bearing exercise › High impact exercise › Strength training › ↓ risk falls by improving balance and agility (↑ muscle mass/ strength) › Help speed up rehabilitation after a fracture › People with severe OP should speak to GP, physiotherapist/exercise physiologist before starting exercise

Answer 436

› Bioavailability - Solubility in intestine – determines potential for absorption › Permeability - Is absorption passive or active? › Transport - Are there carrier or transport proteins? › Assimilation - Biological activity? › Storage - Where? Access to storage site also used as biomarker › Excretion - What is main route for excretion? Enhancing factors? › Sensor and feedback mechanisms - Required to enable homeostasis to continue

Answer 437

› Cells and serum › Distribution – oxygen, nutrients, hormones, etc › Collection of eg waste, etc › Immune function

Answer 438

Haemoglobin, myoglobin - Blood transport and and tissue release of O2 Transferrin and ferritin - Storage and transport forms of Fe Iron-requiring proteins and enzymes - Mitochondrial enzymes eg ferrodoxins - Undergoes Fe3+/Fe2+ conversions in oxidative phosphorylation (e- transport) - In DNA synthesis: Ribonucleotide reductase - Many oxidase enzymes eg - Iron-Sulfur proteins: Xanthine Oxidase (purine catabolism) - Lactoperoxidase (secreted from mucosal glands – natural antibacterial) - Catalase: decomposition of H2O2 to H2O + O2

Answer 439

› ~50mg/kg (3-4g total) › Red cell hemoglobin: 2.5 g (~76%) › RE Stores*: 0.5 g › Myoglobin: 0.3 g › Iron-containing enzymes: 0.2 g › Serum: 0.004 g *Reticulo-endothelial stores: liver, spleen, bone marrow

Answer 440

› Haem - Degradation of globin protein - Food sources containing haemoglobin and myoglobin – animal products › Non-haem - Fe2+, Fe3+ - Plant sources: - fruit, vegetables, legumes - Animal sources - Absorption affected by promoters / inhibitors

Answer 441

Promoters › Contemporaneous meat ingestion (?cysteine effect) › Ascorbic acid (Vit C) - ?conversion of ferric to ferrous Fe; - chelation of Fe in gut lumen – remains more soluble and prevents binding with inhibitory ligands › Other organic acids have some effect eg citric

Answer 442

Inhibitors › Phytates - Found mainly in grain husks - Dose related response between increasing bran in a meal and depression of bioavailability of Fe – inhibition overcome with inclusion of meat and Vit C › Polyphenols - Decrease lipid oxidation - In vitro: potential to increase shelf life of processed foods - In vivo: promoted as healthy component of food - Strong inverse relationship between [polyphenol] and Fe absorption in a food – diverse mechanisms, including chelation - Commonly found in fruits, vegetables, herbs (eg rosmarinic acid), tea (catechins / tannins)

Answer 443

Phases of absorption 1. Luminal - Fe solublised (stomach acid largely), presented to proximal duodenum - Solubility maintained by oxidation state (ferrous (Fe2+) better absorbed), mucin and chelators including ascorbic acid - Inhibitors may be significant 2. Mucosal uptake Depends on Fe binding to brush border of apical cells of duodenum and transport into cell. Haem mechanism unclear non-haem must be Fe2+ - transported by divalent metal transporter (DMT1) 3. Intracellular - Irrespective of source – either stored in ferritin or transported to opposite side of cell and released 4. Release - Oxidised to ferric (Fe3+) form by membrane bound ferroxidase - Released by specialised Fe transporter, ferroportin into portal circulation - Bound in circulation to transport protein transferrin NB – Fe uptake and esp release by mucosal cell are inversely related to the amount of Fe stored in body

Answer 444

Once in circulation.... › Distributed to tissues bound to transferrin › Most goes to bone marrow (for Hb production as part of RBC) › NB RBC survive ~3/12 and are recycled, being engulfed by macrophages or the reticuloendothelial system (RES) › Fe in RES either stored as ferritin or redistributed by transferrin › Most circulating Fe is being recycled › Control of Fe release by ferroportin mediated by hepcidin, which binds to ferroportin, inhibiting Fe release › Numerous modulators react to various stimuli to regulate the circulating [Fe]

Answer 445

Deficiency › Deficiency (nutritional) - Inadequate intake – esp developing countries, poverty, vegetarian, vegan - Low bioavailability - Intake of absorption inhibitors - Avoidance of haem Fe › Physiological - Menstrual blood losses - Pregnancy, repeat pregnancies - Long distance runners - Gut mucosal damage eg enteropathies (eg untreated Coeliac disease) › Pathological losses - Infection eg hookworm - GIT tumour, uterine bleeding, gastric surgery, etc

Answer 446

› ~ 25% in Australian/NZ infants › Caucasian, Asian, Vietnamese, Arabic Associations with deficiency › Premature or low birth weight babies › High intake of cows’ milk › Low intake of haem iron Feeding practices do not match growth rate › Prolonged duration of exclusive breastfeeding › Late introduction of solids or inappropriate solids

Answer 447

› ‘iron deficiency’ – depleted stores but adequate RBC production › ‘Iron deficiency anaemia’ - Inadequate production of RBC - Microcytic (smaller RBC) hypochromic (paler) anaemia › Fatigue - Reduction in Hb and Fe-containing enzymes - Reduced ability to mobilise O2 › Decline in cognitive function - Adults – reduced ability to concentrate (limited data) - Children – intellectual impairment (good data)

Answer 448

› Acute - Vomiting, gastric bleeding › Chronic - Fe accumulates in soft tissuesànecrosis

Answer 449

Iron Toxicity/Overload Haemochromatosis › Uncontrolled intestinal Fe absorption -> tissue overload › Clinical problems: cirrhosis, diabetes, cardiomyopathy, arthritis, testicular failure 1. - - - 2. - Inherited form Autosomal recessive Dysfunctions of several genes coding for Fe sensing and transport: HFE, HFE2 (hemojuvelin), Hepcidin, Transferrin Receptor – frequency homozygous: 0.3%, heterozygous: 12% ‘bronze’ disease – affects most those from European background Acquired Excessive dietary iron e.g., traditional Bantu beverages (iron pots)

Answer 450

= ascorbic acid dificiency can cause scurvy mportant for a healthy immune system: help to produce collagen, used to make skin and other tissues, also helps wound healing

Answer 451

Exceptions are: humans, apes and guinea pigs - Missing gulonolactone oxidase (last enzyme in synthesis) › Absorption is by active transport with high efficiency › ~ 80-90% absorbed at doses of

Answer 452

- Storage - cooking/heat - UV

Answer 453

› Adults: 1.2 - 2.3g › Found in all cells

Answer 454

› Mostly protein-bound - Enzyme activity: 300 enzymes zinc dependent (Zn can be catalytic, co-catalytic, structural) - e.g., oxidoreductases, transferases, hydrolases, lyases, isomerases, DNA/RNA polymerase, alkaline phosphatase, carbonic anhydrase ... › Zinc fingers - transcription factors - gene expression (e.g., iNOS upregulated; Proteasomal ATPase downregulated) › Storage form of insulin

Answer 455

› Absorption - Upper GIT (duodenum mostly) - Saturable and passive › Excretion - Low levels - Faecal excretion – main route – both dietary and endogenous via bile salts - Urine - Endogenous excretion – mostly available though for re-absorption - Sweat, saliva – small amounts - Hair - Semen in males

Answer 456

› Regulate intracellular Zn homeostasis - ZIPs increase cytoplasmic ZN by transporting extracellular Zn into the cell – distribution tissue specific - ZnTs decrease cytoplasmic Zn by promoting extra-cellular Zn efflux

Answer 457

``` › Inhibitory factors - Phytate (dietary fibre) - Polyphenols (tannins eg tea) - Divalent metal ions (eg Ca, Fe, Cu) › Promoters - Citric acid - Small MW organic acids ```

Answer 458

Estimated absorption › 15 % (low) High in unrefined cereals - Phytate : Zn molar ratio > 15 Calcium > 1g › 15-35 % (moderate) Mixed diet - Phytate : Zn molar ratio

Answer 459

› Inadequate intake - Poor diet with low intake Zn-rich foods › Reduced absorption or bioavailability - Eg gut mucosal damage - Interfering substance(s) eg high phytate intake › Increased requirements - Eg growth, pregnancy, lactation › Decreased utilisation - Eg alcoholism › Increased losses - Eg diarrhoea, infection

Answer 460

› Growth retardation › Hypogonadism, infertility (Impaired testis development), delayed sexual maturation › Neurosensory (hyopgeusia, night blindness) and neuropsychiatric disorders (incl behavioural disturbances, confusion, depression) › Skin: acrodermatitis, eczema impaired wound healing › Impaired immunity: (1) innate; (2) T-cell mediated (thymic atrophy) › Alopecia › Children – decreased appetite, poor taste acuity, poor growth

Answer 461

› Serum zinc levels (normal: 11 - 23.0 μmol/L) › Urinary zinc excretion reduced › Blood count may reveal anaemia › Skin biopsy for acrodermatitis

Answer 462

Burden of disease › Est by WHO to be 1 of the 10 biggest factors › Children – contributes up to - 15% diarrhoea deaths, - 10% malaria deaths, - 7% pneumonia deaths › Supplementation of infants, young children - Decreases rates of diarrhoea, pneumonia deaths

Answer 463

› Non-intes#nal losses = 1.3 (urine, 0.6; sweat, 0.5; other, 0.2) › Endogenous intes#nal losses = 2.6 › Intes#nal absorp#on required to replace endogenous losses ≈ 4 › Frac#onal absorp#on (bioavailability): 40% › EAR = 4/0.4 = 10

Answer 464

=folic acid found as tetrahydrofolate in food important for brain function and mental health, aids production of DNA and RNA. importan when tissues are growing quickly

Answer 465

• 1945 Folate isolated from spinach • Folate – derived from word ‘foliage’ • Folic acidàfolate in body • Coenzyme form: tetrahydrofolate THF • THF needed for transfer of one-carbon units • THF acts as an acceptor or donor of one-carbon units, specifically in amino acid and nucleic acid metabolism (RBCs)

Answer 466

• Megaloblastic anemia – – RBCs enlarged, nuclei larged but reduced chromatin (because can’t double their DNA to divide due to impaired synthesis of thymidylate) • Anemiaàheart failureàDEATH • Infertility • Diarrhoea

Answer 467

– Abnormal development of the neural tube (CNS) – Spina bifida • failure of the lower neural tube to close during embryogenesis • infantile paralysis- lack of protection of the spinal cord – Anencephaly • failure of the upper neural tube to close during embryogenesis • absence of all/most of the brain

Answer 468

``` • High sources – Leafy vegetables (cabbage 230-430, spinach 140) – Liver (260) – Peanuts (110) • Medium sources – Peas (80) – Egg yolk (50) – Oranges (40) – Wholemeal bread (30) • Low sources – Meat (3) – Milk (0.3) ```

Answer 469

= cobalamin usually contains CN as the R group important for the nervous system, for making red blood cells, and helps in the production of DNA and RNA

Answer 470

Large complex structure containing a Cobalt ion (red colour)

Answer 471

Coenzyme for 3 enzymes: – Mitochondrial methylmalonyl-CoA mutase • Cobalamin has a 5’deoxyadenosyl group attached to cobalt atom • metabolism of propionate & some amino acids • methylmalonyl-CoA → succinyl-CoA – Cytosolic methionine synthase • Cobalamin has a methyl group attached to cobalt atom • Metabolism of 1 carbon • 5-Me-THF + homocysteine → methionine – Leucine mutase • First step in the degradation of leucine

Answer 472

• Megaloblastic anaemia – identical to folic acid deficiency – large red blood cells – white cells, large with low nuclear density – due to decreased purine and pyrimidine synthesis, less DNA biosynthesis, less cell division • Pernicious (fatal) anaemia – due to lack of IF • Neuropathy – Accumulation of propionate in nerve tissue – Subacute combined degeneration (SCD)

Answer 473

=menadione all K vitamins are menadione or derivatives helps blood clot properly and plays a key role in bone health. newborns receive Vit K injections to prevent bleeding

Answer 474

Vitamin K1: phylloquinone • synthesised in green plants Vitamin K2: menaquinones (MK 1-14) • made by gut bacteria • bioavailability ? Vitamin K3: menadione • synthetic, water soluble • no longer used

Answer 475

• cofactor for γ-glutamyl carboxylase | – post-translational carboxylation of glutamate to γ- carboxyglutamate so it can bind calcium

Answer 476

Vitamin K is common in food | Bacteria make vitamin K in the large intestine Vitamin K is reused in a conservation cycle

Answer 477

``` Proteins that use this mechanism (have γ-carboxyglutamate residues): – Clotting Factors: prothrombin (II), VII, IX, X – Anticlotting factors: Protein C and S – Coagulation Proteins M and Z – Bone protein: Osteocalcin ```

Answer 478

Why newborn infants may be deficient in vitamin K • Vitamin K levels in breast milk are low • Bacteria to make vitamin K in the large intestine may not yet be ready • The vitamin K conservation cycle may not be developed Can cause intracranial haemorrhage, resulting in severe and permanent brain d

Answer 479

With parental consent, newborns receive vitamin K supplement as one of the following: – 1 mg (2.2 μmol) intramuscular injection at birth – 3 oral doses

Answer 480

``` B1 Thiamin B2 Riboflavin B3 Niacin B5 Pantothenic acid B6 Pyridoxine B7 Biotin B9 Folate B12Cobalamin ```

Answer 481

``` • Active form is as a COENZYME COENZYME = a substance that enhances the ac9on of an enzyme • Principle Functions: – Energy production from carbohydrates, fats and protein – Synthesis of neurotransmitters – Conversion of amino acids – Synthesis of fatty acids and hormones – Antioxidant protection ```

Answer 482

=thiamin can also occur in pyrophosphate ester form used to keep nerves and muscle tissue healthy. also important for processing of CHO and some proteins

Answer 483

• Coenzyme forms: thiamin pyrophosphate (TPP) thiamin triphosphate (TTP) • Coenzyme for decarboxylases eg: • Oxidative decarboxylation – In glycolysis and TCA cycle – Of branched chain amino acids • Transketolase reactions in the pentose phosphate pathway

Answer 484

RDA 1.1-1.2mg / day adults In small but sufficient quantities in most nutritious foods High in pork products, sunflower seeds, pasta, bread (fortified) Destroyed by: heat, leached out into cooking water

Answer 485

• Inadequate intake • Chronic alcoholism – Thiamin absorption is impaired – Decreased food intake – Increased excretion • High (inadvertant) intake of thiaminase eg raw fish • “refeeding syndrome” in hospitalised patients

Answer 486

``` Peripheral neuropathy • longest nerves affected first - long limbs – legs • loss of sensation Enlarged heart, cardiac failure Weight loss Muscular weakness - can’t walk, foot drop Poor short term memory ```

Answer 487

Acute Oedema Raised jugular vein pressure

Answer 488

=riboflavin excess turns urine bright yellow important for body growth, red blood cell production, and keeping the eyes health. also helps processing of CHO

Answer 489

• Coenzyme forms: – Flavin Adenine Dinucleotide (FAD) – Flavin Mononucleotide (FMN) • Riboflavin coenzyme activity regulated by Thyroid Gland

Answer 490

β-oxidation of fatty acids in mitochondria

Answer 491

• Inflammation of membranes of eyes, mouth, skin, gastrointestinal tract • Sensitivity to light • Cracks at side of mouth (angular cheilosis) • Anemia • Retarded growth in children

Answer 492

= nicotinic acid and nicotineamide niacin is collective name for these compounds helps with digestion and digestive system helath. also helps with the processing of CHO.

Answer 493

Vit B3 Niacin

Answer 494

Coenzymes are: | NicoKnamide Adenine DinucleoKde (NAD) NicoKnamide Adenine DinucleoKde Phosphate (NADP

Answer 495

• NAD – Energy production from carbohydrate, fat and proteins – Like FAD, NAD is an acceptor of electrons to form a reduced form NADH2 • NADP – Biosynthesis of fatty acids and cholesterol

Answer 496

• Dietary intake of: – nicotinic acid and nicotinamide – precursor amino acid (tryptophan) • Synthesis from tryptophan in the liver via the kynurenine pathway – 60 mg tryptophan 1 mg niacin – Synthesis proportional to intake of Trp • Ratio of dietary intake:synthesis is ~ 1:1

Answer 497

* Niacin deficiency also known as the 4D’s * Dermatitis * inflammation, similar to sunburn • Casal’s collar * Diarrhoea - also inflamed tongue (glossitis) * Delirium or dementia – in severe cases * Death

Answer 498

• Niacin is obtained either from • preformed niacin and/or protein, specifically Tryptophan • dietary protein contains ~ 1% Trp • 60 mg Trp = 1 mg Niacin • Niacin equivalents (NE) in mg = Niacin + protein (g) x 1 x 1000 100 60 = Niacin + Tryptophan (mg) 60

Answer 499

* RDI: 14-16mg/d Niacin Equivalents * Niacin/nicotinic acid 35mg/d causes flushing – 3g/d reduces LDL but causes liver damage * Niacinamide/nicotinamide >2g/day reduces insulin sensitivity

Answer 500

=pentothenic acid can also occur in pyroophosphate ester important for manufacturing RBC and maintaining a healthy digestive system. also helps process CHO

Answer 501

* 1933 Identified as a growth factor for yeast | * Forms a large part of the Coenzyme A molecule

Answer 502

* Essential for reactions that generate energy from carbohydrates, fats and proteins * Synthesis of cholesterol and steroid hormones (melatonin) * Synthesis of acetylcholine, heme * Metabolism of drugs and toxins * Synthesis of fats in the myelin sheath * Synthesis of phospholipids

Answer 503

``` • Deficiency is rare, reported in severely malnourished humans • Good sources: whole grains, nuts and seeds, legumes, most vegetables • Require ~5mg/d • Also made by bacteria in colon • SUPPLEMENT forms: pantothenol calcium pantothenate sodium pantothenate Panthene – cholesterol lowering drug ```

Answer 504

= pyridoxal phosphate active form in mammalian tissues helps make some brain chemicals, needed for normal brain function, also helps make RBC and immune system cells.

Answer 505

• Discovered in 1930s • Several forms (vitamers): pyridoxine, pyridoxal, pyridoxamine • Coenzyme form: pyridoxal phosphate PLP • Large stores in muscle

Answer 506

• Required for many biochemical reactions including: – Glycogenolysis – glycogenàglucose – Gluconeogenesis – amino acidsàglucose – Conversion of tryptophan into niacin, serotonin, dopamine, GABA and norepinephrine – Transamination – synthesis of non essential amino acids – Synthesis of heme – Synthesis of nucleic acids (DNA/RNA) – Conversion of homocysteine to cysteine – reducing CVD risk

Answer 507

• RDA 1.3 – 1.7mg/day • Deficiency is rare • Found in many foods – Meat, spinach, bananas, potatoes are good sources • Fortified in refined grains • PLP is destroyed by acetalaldehyde (product of alcohol metabolism) Symptoms of B6 Deficiency: Depression Confusion Abnormal brain waves Convulsions

Answer 508

=Biotin produced by intestinal bacteria needed for metabolism of various compounds, often recommended for strengthening hair, but evidence is variable.

Answer 509

• From the Greek word bios meaning life • Discovered in 1930s • Biotin deficiency linked with skin problems in animals fed only egg whites (egg white injury) Co-enzyme form are: acetyl Coa carboxylase, pyrubate carboxylase, methlcrotonyl coa carboxylase and propionyl coa carboxylase.

Answer 510

* Biotinidase (biotin transferase function) * Addition of biotin to other molecules • modification of nuclear histone proteins * potential role for biotin in gene expression • DNA replication and transcription

Answer 511

• Rare except in: – Intravenous feeding if biotin not added – Raw egg white consumption – Lack of biotinidase – releases biotin from proteins • Symptoms: • Elevated serum cholesterol • Scaly dermititis (nose, eyes, mouth, genitals) • Fatigue, nausea, anorexia • Alopecia, depression, hallucinations

Answer 512

• 25-30mg / day • Widely distributed in foods, but mostly in low concentrations • good sources (20-100 μg/100g): liver, kidney, egg yolk, cereals, Brewer’s yeast, soybeans, peanuts, walnuts, molasses • Toxicity rare – 5 mg/day tolerated without side-effects