Nutrition Flashcards
Give a general description of Vitamin A
- collectively called retinoids
- Retinol: transport and storage form of vitamin A
- 11-cis retinal is required for vision
- Retinol and retinal can be easily interconverted.
- Retinoic acid: epithelial growth and differentiation. It has steroid hormone like effect.
Describes the steps of the absorption and transport of Vitamin A
Diet contain Retinol esters -> hydrolysis by intestinal mucosa releasing Retinol and free fatty acids -> re-esterfication and secretion in chylomicrons which are taken up by the liver where it is stored -> plasma Retinol binding protein in the liver transports to extra hepatic tissues -> tissues contain cellular Retinol binding protein that carries Retinol into the cell
List the sources of Vitamin A
- Liver, kidney, butter and cream products; egg yolks
- Yellow vegetables and fruits ( dietary pro vitamin form: B-carotene)
What are the functions of Vitamin A?
- Vision: 11 cis retinal is a component of rhodopsin (visual pigment). Visual cycle req isomerization b/w cis and trans-retinal
- Maintenance of specialized epithelia, esp mucus secreting cells (Retinoic acid)
- Growth (Retinoic acid)
- Reproduction (Retinol)
Describe the mechanism of action of Retinoic acid in epithelia cells.
1) Retinol enters target cell and is oxidized to Retinoic Acid in cytosol
2) Retinoic Acid moves from cytosol into nucleus with help of Retinoid Binding Proteins
3) Retinoic Acid binds to nuclear receptors forming an activated receptor complex
4) Retinoic acid-receptor complex binds to chromatin activating the transcription of specific genes (keratin)
Describes the steps in the visual cycle pathway
- Retinol (transported in blood in the form of all-trans Retinol) enters retinal pigment epithelium.
- Esterfied to All-trans retinyl ester
- becomes 11-cis Retinol
- oxidized to 11-cis Retinal
- 11-cis retinal enters rod cell where it combines with opsin to form rhodopsin (visual pigment).
- absorption of light photon catalyzes isomerization of 11-cis retinal to all-trans Retinal triggering eventual signal for vision.
- Opsin becomes available again and All-trans retinal eventually becomes all-trans Retinol.
- all trans Retinol goes back to retinal pigment epithelium to renter cycle.
What causes Vitamin A deficiency?
Dietary deficiency most common - fat free diet
Fat malabsorption
What are some signs and symptoms of Vitamin A deficiency?
- Night blindness
- Xerophthalmia
- Bitot’s spots
- Keratomalacia
- increased risk of pulmonary infections
- immune deficiency - weakened innate immunity
What is Night blindness and what is the cause?
Earliest of the symptoms of Vitamin A deficiency.
- inability to see Dim light
- reversible
What is Xerophthalmia and what is the cause?
Vitamin A deficiency that produces dryness of the conjunctiva and cornea.
Reversible
What treatment is Retinoic acid given for?
Acne treatment, especially topical form
What is all-trans Retinoic acid used in treatment of?
Acute promyelocytic leukemia
What can hypervitaminosis of Vitamin A cause?
- Raised intracranial pressure leading to headaches - may mimic brain rumors
- Dry and pruritic skin
- enlarged liver
- can cause spontaneous abortions and congenital malformations in the fetus during pregnancy.
What is the name for vitamin D found in plants?
Ergocalciferol (D2)
What is the general name for vitamin D found in animals?
Cholecalciferol (D3)
What is the name of the precursor for Cholecalciferol synthesis in skin?
7-Dehydroxycholesterol
(intermediate in cholesterol synthesis)
(Cholecalciferol is Vitamin D3)
What are other names for the active form of Vitamin D?
- Calcitriol
* 1,25 dihydroxy cholecalciferol
In Vitamin D synthesis, what is the first step?
7-dehydrocholesterol in the skin is activated by sunlight to form Cholecalciferol.
Or
Cholecalciferol is taken in through diet.
Regarding the steps of Vitamin D synthesis, what happens to Cholecalciferol?
Goes to liver (from skin or diet) and, through enzyme 25-Hydroxylase, becomes 25-hydroxycholecalciferol. Next goes to kidney.
Regarding the steps of Vitamin D synthesis, what happens in the kidney?
25-hydroxycholecalciferol (from liver) is converted into 1,25-dihydroxycholecalciferol/Calcitriol (active form of vitamin D) by the enzyme: 1-Hydroxylase
Which is the regulated step in Vitamin D synthesis and how is it regulated?
25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol step in kidney.
1-Hydroxylase is activated by:
1) Parathyroid Hormone
2) low calcium levels
1-Hydroxylase is inhibited by:
1) Calcitriol
What occurs once 1,25-dihydroxycholecalciferol (Calcitriol) is made?
(Mechanism of action)
It binds to intercellular receptor proteins
What happens after Calcitrol binds to intracellular receptor proteins of the target cell?
Calcitrol-receptor complex interacts with DNA in nucleus and can either stimulate or repress gene expression.
What effect does Calcitriol have on the intestine?
It stimulates intestinal absorption of calcium and phosphate by increasing synthesis of a specific calcium binding protein.
What effect does Calcitriol have on bone?
It stimulates the mobilization of calcium and phosphate from the bone in the presence of parathyroid hormone.
What effect does Calcitriol have on the kidneys?
It inhibits calcium excretion by stimulating parathyroid dependent calcium reabsorption.
What are the causes of Vitamin D deficiency?
- nutritional deficiency - decreased intake / fat malabsorption
- inadequate exposure to sunlight (common during winter)
- chronic renal disease, chronic liver disease results in decreased hydroxylation of vitamin D
What is Rickets?
Vitamin D deficiency in children.
How does Rickets effect calcium absorption in the diet?
Calcium absorption is decreased, causing:
- increased parathyroid hormone release which leads to
- demineralization of bone.
What are the manifestations of Rickets?
- Soft pliable bones
- Bow- leg deformity
- Rachitic rosary (overgrowth at costochondral jxn)
- Pigeon chest deformity
- frontal bossing
- swelling of wrists
What is Osteomalacia?
Vitamin D deficiency in adults
What are the manifestations of Osteomalacia?
Bones are demineralized and thus susceptible to fracture.
What can cause Osetomalacia?
Dietary deficiency of vitamin D, renal failure or liver disease.
What is name for the active form of Vitamin E
Alpha tocopherol
What is the primary role of Vitamin E?
Anti-oxidant
When is vitamin E deficiency typically seen?
Patients with fat malabsorption.
rare
How is Vitamin E deficiency manifested?
1) Hemolytic Anemia (abnormal cellular membranes)
2) Reduced deep tendon reflexes and gait problems due to anoxal degeneration.
What is the name for Vitamin K in plants?
Phylloquinone
-dietary source
What is the name for Vitamin K in bacteria?
Menaquinone
-intestine
Which clotting factors are Vitamin K required for?
Hepatic synthesis of the mature clotting factors:
Prothrombin (II) VII IX X Proteins C and S
Which enzyme does Vitamin K serve as a cofactor for?
Liver microsomal y-carboxylase
Which amino acid residues do Vitamin K dependent y-carboxylase act upon?
Glutamic acid residues
(y-carboxylation forms a mature clotting factor that contains y-carboxyglutamate (Gla) and is capable of subsequent activation)
Why is y-carboxylation important for the activation of clotting factors?
y-carboxylation allows Ca2+ binding because of two adjacent negatively charged carboxylate groups.
What does the clotting factor calcium complex bind to?
Phospholipids in the plasma membrane.
How vitamin K deficiency manifested in neonates?
Hemorrhagic disease of the newborn
- Bleeding at various sites in the body including skin, umbilicus and viscera
- Intracranial bleeding
Sterile intestines of the newborn - no synthesis of Vitamin K
How is neonatal vitamin K deficiency treated?
Routine intramuscular injection of Vitamin K for all newborns.
What is the effect of warfarin administration?
1) Vitamin K antagonist
2) Warfarin blocks the activity of liver epoxide reductase and prevents regeneration of reduced vitamin K (no recycling of Vitamin K)
3) There is reduced y-carboxylation of clotting factors and a delay in clotting (increased prothrombin time or INR)
What causes vitamin K deficiency in adults?
Fat malabsorption and prolonged use of broad spectrum antibiotics
How is vitamin K deficiency manifested in adults?
Bleeding disorder characterized by:
- Hematuria
- Melena (black tarry stools)
- Ecchymoses (bruises)
- Bleeding from gums
What is another name for Vitamin C?
Ascorbic acid
What is vitamin C’s role in collagen synthesis and wound healing?
- Required for collagen cross-linking.
- Acts as a coenzyme for hydroxylation of proline and lysine residues in collagen
What is vitamin C’s role in iron absorption?
Reduces iron to the ferrous state in the stomach
How does vitamin C acts as a water soluble anti-oxidant?
- Scavenger of free radicals
- Regenerates anti-oxidant form of Vitamin E
Vitamin C deficiency leads to?
Scurvy
- due to decreased hydroxylation of collagen; results in a fewer number of Hydrogen bonds in collagen.
What are the symptoms of Scurvey?
1) Perifollicular hemorrhages (fragile blood vessels)
2) Sore, spongy gums - bleeding from gums
3) Loose teeth
4) Bleeding into joints
5) Frequency bruising
6) Impaired wound healing
Which vitamin deficiencies cause bleeding from gums?
Vitamins K and C
Which are the fat soluble vitamins?
A,D,E,K
Which are the energy-releasing vitamins?
1) Thiamine (Vitamin B1)
2) Riboflavin (Vitamin B2)
3) Niacin (Vitamin B3)
4) Biotin
5) Pantothenic acid
What is another name for Vitamin B1
Thiamine
What is the coenzyme form of Vitamin B1?
Thiamine Pyrophosphate (TPP)
Which enzymes are TPP dependent?
Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, branched chain alpha-keto acid dehydrogenase, and transketolase
Which enzyme in the pentose phosphate shunt uses TPP?
Transketolase
Ribose 5-P to Glyceraldehyde 3-P; vice-versa
Which types of foods lack Vitamin B1?
Refined foods such as:
- Polished rice
- White flour
- White sugar
Describe the cause of dry Beri Beri
Thiamine deficiency
- Paralysis due to polyneuropathy resulting from disruption of motor, sensory, and reflex arcs.
Describe the cause of wet Beri Beri
Thiamine deficiency leading to cardiac faliure
What are the symptoms of Wernicke-Korsakoff?
1) Ophthalmoplegia and nystamus (to and fro movement of eyeballs)
2) Ataxia
3) Confusion
4) Disorientation
5) loss of memory
6) Confabulation
What is another name for Vitamin B2?
Riboflavin
What are the coenzyme forms of Riboflavin? (Vit B2)
- Flavin mononucleotide (FMN)
- Flavin dinucleotide (FAD)
What is the function of Riboflavin (VitB2)?
Participates in oxidation-reduction reactions of TCA cycle, beta oxidation (Succinate D.H, PDH, Acyl CoA DH…)
What are the signs and symptoms of Riboflavin deficiency?
- Cheilosis
- Glossitis
- Facial dermatitis
What is Cheilosis?
- Riboflavin deficiency.
- Pallor, cracks & fissures @ mouth angles
What is glossitis?
- Riboflavin deficiency
- tounge atrophy & inflammation
What is another name for Vitamin B3?
Niacin
What are the coenzyme forms of Vitamin B3?
- NAD+
- NADP+
How is Vitamin B3 used in treatment of type IIb hyperlipoproteinemia?
Inhibits lypolysis -> adipose tissue = free F.A. reduction
What are the manifestations of Niacin deficiency?
- Pellagra (necklace-like skin damage)
- Death
What characterized Pellagra?
3 D’s:
1) Dermatitis
2) Diarrhea
3) Dementia
What amino acid is used to synthesize NAD+ AND NADP+?
Tryptophan
What can corn based diets cause?
Pellagra
- Corn = no niacin / tryptophan
Which disease can cause pellagre-like symptoms?
Hartnup’s disease
- supplement = niacin
What else, besides nacin deficiency, can cause Pellagra?
Carcinoid syndrome
What is another name for Biotin?
Biocytin
What is Biotin a prosthetic group for?
Carboxylation reactions
What protein inhibits Biotin absorption?
Avidin
- found: raw egg whites
What is Multiple Carboxylase Deficiency
Inherited deficiency of the incorporation of biotin
Which enzymes require Biotin?
1) Pyruvate Carboxylase
2) Acetyl-CoA carboxylase
3) Propionyl-CoA carboxylase
Whats another name for Vitamin B6?
Pyridoxine
What are precursors for pyridoxal phosphate (PLP)?
Pyridoxine Pyridoxal Pyridoxamine (collectively = Vit B6)
Which enzyme in heme synthesis needs PLP
ALA Synthase (condensation)
Which reactions do PLP act as a co-enzyme for?
1) Transamination (amino acid metabolism)
2) Amino Acid decarboxylation (synthesis of neurotransmitters)
3) Condensation
4) Conversion of homocysteine and cysteine
What are children with homocystinuria supplemented with?
Vitamin B6
What inactivates pyridoxine?
Isoniazid (Anti-TB drug)
What are sign’s and symptoms of pyridoxine deficiency?
1) Microcytic anemia
2) Peripheral neuropathy
3) Increased risk of cardiovascular disease (homocysteine = high)
4) Seizures
What is another name for Vitamin B12?
Cobalamin
Which reactions require Vitamin B12?
1) Homocysteine -> Methionine (Homocysteine methyltransferase)
- Methytetrahydrofolate -> Tetrahydrofolate
2) Methylmalonyl CoA -> Succinyl CoA
(Methylmalonyl CoA mutase) (odd # F.A. degradation)
What happens to folate in B12 deficiency?
Folate trap - Methyltetrahydrofolate
- Result: macrocytic anemia
How does B12 deficiency affect methylmalonate?
Methylmalonate accumulation -> neurological manifestations
What is given to patients with inherited methylmalonic aciduria?
Vitamin B12
Why do vegans have a high risk of developing B12 deficiency?
- Synthesized only by micro-organisms;
- not present in plants.
Which cells produce intrinsic factor?
Gastric Parietal cells
Why is intrinsic factor necessary?
B12 absorption.
- Lack of = pernicious anemia
What are signs and symptoms of Vitamin B12 deficiency?
Macrocytic anemia
Neuropsychiatric symptoms
What are signs of macrocytic anemia?
- Macrocytes in peripheral blood film
- Megaloblasts in bone marrow
- occurs due to folate deficiency
What neuropsychiatric symptoms stem from B12 deficiency?
- Myelin degen in motor and sensory pathways due to methylmalonyl CoA accum.
- present in absence of anemia
What plays a key role in one-Carbon metabolism?
Folic Acid
In what form do most cells receive folate?
Methyl THF
- methyl THF -> THF needs B12.
How does Megaloblastic anemia occur?
Diminished synthesis of purines & pyrimidines -> inability of cells to synthesize DNA -> delayed mitosis = larger cells
What are causes of Folic acid deficiency?
- Lack of leafy green vegtables
- Impaired absorption
- Increased req as in pregnancy
- Methotrexate
- Folate trapping
How should megaloblastic anemia be treated?
Combination of folic acid & Cobalamin
What effect does folic acid deficiency during pregnancy cause?
Neural tube defects
Tyrosine needs the co-factor Copper for?
Melanin synthesis
Dopamin B-hydroxylase needs the co-factor Copper for?
Neurotransmitter synthesis
How is ingested copper transported to the liver?
Albumin
Aged ceruloplasmin is taken up by the liver from the plasma, endocytosed and degraded and…
Copper is secreted into bile
What are signs and symptoms of Copper deficiency?
- Microcytic anemia
- Vascular tissue degredation
- Defects in hair
Why does copper deficiency contribute to microcytic anemia?
Ceruloplasmin (ferroxidase) req. 4 iron metabolism
Why does copper deficiency contribute to the degradation of vascular tissue?
Dec. lysyl oxidase activity
What causes Menke’s syndrome?
x-linked GI tract copper absorption defect
What is a characteristic of Menke’s syndrome?
Hair: Twisted, grayish, kinky
What can copper deficiency lead to?
- Aneurysms
- Cerebral dysfunction
What is Wilson’s disease?
Autosomal recessive copper metabolism disorder
What characterizes Wilson’s disease?
Copper accumulation -> toxic
- liver, brain, eye
What chromosome does Wilson’s disease affect?
Chromosome 13
Where is Wilson’s disease found to affect?
Copper transporting ATPase - Liver
What is the copper transporting ATPase in liver needed for?
- copper -> ceruloplasmin (attach)
- Copper excretion into bile
What causes Kayser Fleischer (KF) rings?
Deposition of copper in the cornea
What is the importance of Iron?
- Heme synthesis
- Redox rxn
What is iron’s role in Heme synthesis?1
Incorp into heme of heme containing proteins
What happens when your body’s iron stores are high?
Less Fe absorbed by intestines
Where is heme iron derived from?
Meat
Where is inorganic iron derived from?
Vegtables
What state does inorganic iron need to be in in order to be taken up into the intestinal mucosal cells?
Ferrous
Which is absorbed more effectively, heme iron or inorganic iron?
Heme (meat) iron
Where is ferric iron changed to ferrous iron?
Stomach (low pH and vit C)
What is the transport protein for ferric iron in blood plasma?
Transferrin
Where is iron stored and in what form?
- Liver & RES
- Ferritin & hemosiderin (ferric)
What is another name for ceruloplasmin?
Ferroxidase
What is the role of ceruloplasmin?
- Ferrous ion release from intestinal cells
- forms ferric iron (transport)
- Copper carrying protein
Who are typically susceptible to iron deficiency?
Infants
pregnant women
blood donors
What are the clinical features of iron deficiency?
1) Hypochromic microcytic anemia
2) Fatigue and pallor
3) Weakness
4) Brittle nails
5) Pica
What is pica?
Appetite for soil
- iron deficiency
What is Hereditary Hemochromatosis?
Autosomal recessive
- HFE gene defect
- excessive iron absorption -> accum in liver and pancreas
What is the role of HFE gene?
-Protein regulates iron absorption by regulating interaction of transferrin receptor to transferrin.
How does excess iron damage tissues?
- DNA damage
- Lipid peroxidation through free radicals
What are the clinical features of Hereditary Hemochromatosis?
- 40 y/o M
- Liver damage: cirrhosis; hepatocellular carcinoma; hepatomegaly
- Diabetes: pancreas destruction
- Cardiac dysfunction
- Acute synovitis (arthritis)
- Bronze skin
- Testicular atrophy (dec FSH/LH sec)
- Hair loss
- Memory loss
- Vertigo
What is the cause of microcytic anemia?
-Reduced heme synthesis
-Lead poisoning
-Deficiency of:
Iron
Copper
Pyridoxine
What is the cause of macrocytic anemia?
-Reduced cell division
-Deficiency of:
B12
Folate
What does Copper form in the liver?
Ceruloplasmin
In general, what types of reactions is copper an important cofactor for?
Redox rxns
What specific enzymes needs copper as a co-factor?
1) Cytochrome C
2) Superoxide Dismutase
3) Lysyl Oxidase
4) Tyrosinase
5) Dopamine B-Hydroxylase
Can essential molecules be synthesized at all or at a rate compatible with need?
No
What are the 3 components of the Daily Energy Expenditure (DEE)?
1) Energy for BMR or RMR
2) Physical activity
3) Energy req to process food. (induced thermogenesis)
What is RMR?
Resting metabolic rate
- energy expenditure by individual in resting, post-absorptive state
How much of total energy expenditure in a sedentary individual is represented by RMR?
50-70%
How does gender play a role in affecting RMR?
Male = 20% higher than female
How does body temperature play a role in affecting RMR?
Inc. with temp. inc. (fever)
How does environmental temperature play a role in affecting RMR?
Cold temp = High RMR
What effect does HYPERthyroidism have on RMR?
Increase
How does pregnancy and lactation affect RMR?
Increase
How does age affect RMR?
Decrease
What is diet-induced thermogenesis (DIT) also known as?
- Thermic effect of food (TEF)
- Specific dynamic action (SDA)
What does diet-induced thermogenesis (DIT) represent?
Req. energy to digest, absorb, distribute and store nutrients
What are the three main categories of macronutrients provided by diet?
Fat
Protein
Carbohydrate
(also ethanol if consumed)
What are minor or micronutrients?
Vitamins and minerals
How much kcal/g does Fat produce?
9 kcal/g
How much kcal/g do carbohydrates produce?
4 kcal/g
How much kcal/g does protein produces?
4 kcal/g
How much kcal/g does alcohol produce?
7 kcal/g
How are carbohydrates classified?
- Simple sugars: monosaccharides and disaccharides
- Complex sugars: Polysaccharides
- Fiber
What are the principle monosacharides in food?
Glucose and Fructose
Which foods are abundant in glucose?
Fruits, sweet corn, corn syrup, honey
Where is free fructose found?
together with free glucose and sucrose - honey and fruits
Which are the most abundant disaccharides?
Sucrose
Lactose
Maltose
What does sucrose consist of and where is it found?
Glucose + fructose
- table sugar
- molasses
- corn syrup
What does lactose consist of and where is it found?
Glucose + Galactose
- milk
What does Maltose consist of and where is it found?
Glucose + Glucose
- beer
- malt liquor
Polysaccharides are complex carbohydrates, often polymers of…
Glucose
What is starch?
Polysaccharide found in plants
What are the sources of polysaccharides?
Wheat and other grains Potatoes Dried peas Beans Vegetables
What does the glycemic index represent?
Quantitates time course - postprandial blood glucose rise and decline
What effect do high glycemic index carbohydrates have?
Faster serum glucose rise/ steeper decline (than low G.I. carbs)
What does fiber consist of?
Non-digestible carbohydrates
What are some examples of fiber containing compounds?
Cellulose
Lignin
Pectin
How does dietary fiber add bulk to diet?
Absorbs 10-15X own weight, drawing water into intestine -> increase in bowl motility.
How are the binding properties of dietary fiber beneficial?
Dec. absorption of toxic compounds and certain carcinogens
How does dietary fiber effect postprandial blood glucose concentration?
Reduce
What effect does dietary fiber have on absorption of dietary fat and cholesterol?
Decrease
also inc fecal loss of cholesterol
What do dietary fibers decrease risk for?
Constipation
Hemorrhoids
Diverticulosis
Colon cancer
Why is excess fiber not recommended?
Can dec. absorption of fat-soluble vitamins and bind to some trace elements (Zn2+)
What percentage of dietary lipids are made up of TAGs?
> 90%
How are TAGs obtained from plant sources different from those obtained from animal sources?
Plant = more unsaturated fatty acids
except coconut oil and palm oil
What type of saturation do unsaturated fats in plant dietary lipids contain?
Mono or polyunsaturated
Corn oil and soybean oil are rich in what type of fat?
Polyunsaturated
Olive oil and canola oil are rich in what type of fat?
Monounsaturated
Margarine is described as…
A mixture of vegetable oils with varied composition of unsaturated fats -> hydrogenation for stability
When does arachidonic acid become essential?
When Linoleic acid is insufficient
Essential fatty acids are required for the synthesis of..
eicosanoids
What characterizes a deficiency of essential fatty acids?
- Scaly dermatitis
- Hair loss
- Poor wound healing
People should aim to decrease _______ fats while increasing _____ or ______ fatty acids.
Saturated
Mono-unsaturated
Poly-unsaturated
When do arginine and histidine become required?
during rapid tissue growth as in childhood or recovering from illness
Regarding biological value, how do proteins from animal sources differ from those from plants?
Animal = higher value Plant = lower value
What is an example given of how combination of plant derived proteins can provide complete protein requirement?
Wheat (Lys-deficient, Met-rich) + kidney beans (Met-rich, Lys-poor) = complete protein
What is nitrogen balance?
Amount of N consumed = N excreted in urine, sweat and feces
An individual is typically in a state of negative N balance when…
The body has to degrade tissue protein in order to fulfill requirements
Serum cholesterol levels have a strong correlation with what?
Vascular disease
How does reducing dietary cholesterol effect serum cholesterol levels?
Not much affect
How does a person reduce serum cholesterol levels?
Reduce saturated fatty acid intake
Increase mono and polyunsaturated fatty acids
How does one decrease de novo synthesis of cholesterol?
Statins
What metabolic effects do mono-unsaturated and poly-unsaturated fatty acids have?
Decrease LDL and HDL
-Through arachidonic acid
Leptin acts upon what part of the brain?
Hypothalamus
What does leptin regulate?
Inflammatory response, blood pressure, and bone density
Leptin is produced in what tissue?
Adipose
Leptin is produced proportionally to what?
Fat cell density
Leptin plays a role in what?
Appetite supression
Weight gain
Energy expenditure
What part of the brain does Insulin act upon?
Hypothalamus
How is insulin similar to leptin?
Dampens appetite by acting on hypothalamaus
What is Ghrelin?
A peptide hormone secreted by endocrine cells of stomach
What effect does Ghrelin have?
Increases release of neuropeptide Y (NPY) which in turn enhances appetite and food intake.
How is Ghrelin regulated?
Activated by fasting and low glucose and inhibited by high glucose
What is the effect of Cholecystokinin (CKK)?
Along with PYY, cause satiety during meal & transmit signal to hypothalamus.
How can a rough estimate of RMR be obtained?
Assuming it is 24kcal/day/kg of body weight
How much additional % of RMR should a person consume if they are sedentary?
30%
How much additional % of RMR should a person consume if they are active?
100%
How do you calculate total daily energy expenditure (DEE) /day for a sedentary person?
RMR + .3RMR + .1RMR or
1.4xRMR
How do you calculate total daily energy expenditure (DEE) / day for an active person?
RMR + RMR + .1RMR = 2.1xRMR
Calculate the exact weight of nutrients needed to meet DEE req. for a person consuming 2352kcal/day assuming 50 % carb, 30% fat, and 20% protein
Carbs: 0.5(50%) x 2352
Fat: 0.3(30% x 2352
Protein: 0.2.(20%) x 2352
What does Albumin tests indicate in regards of nutritional status?
Low levels = malnutrition
Tests for serum transferrin levels reflects
Acute protein deficiency
What is pre-albumin serum level tests used for?
short-term (3 days) changes in nutritional status, declines rapidly with acute stress or illness
What does pre-albumin transport?
Thyroxine
Retinal-binding protein
Which is the most accurate measure for estimating DEE?
Indirect Calorimetry test aka Respiratory Quotient (RQ)
What does an RQ test provide information on?
Substate (carbs, fats, proteins) utlization
What does the Respiratory Quotient equal?
RQ = Volume of CO2 expired / volume of O2 consumed
What does a respiratory quotient (RQ) value less than 0.85 indicate?
Protein and fat oxidation, therefore provide more carbohydrates
What does a respiratory quotient (RQ) value greater than 1.0 indicate?
Excess carbohydrate oxidation, provide more lipids
What is a general description/definition of obesity in relation to BMI?
More than or equal to 30 kg/m2
BMI strongly correlates with
total fat content in adults
How do you calculate obesity?
BMI = Weight (kg) / Height (m2)
What is a “normal/healthy” BMI range?
18.5 - 24.9
What does having a wait to hip ratio greater than 1 in men and women increase?
Health risks
What are three methods to assess body fat content?
Skin fold measurements
Bioelectric impedence
Underwater weighing
What are 3 metabolic effects of obesity?
Dyslipidimia
Glucose intolerance
Insulin resistance
What does obesity increase the risk for?
Athlerosclerosis Cardiovascular disease stroke diabetes cancer
What do visceral and abdominal fat contribute to higher levels of?
higher VLDL in blood
Where do fatty acids released from subcutaneous fat go before they reach the liver?
General circulation -> used up by muscle -> reach liver
Apple shaped distribution of fat means higher levels of _____ fat.
Visceral
Pear shaped distribution of fat means higher levels of _____ fat.
Subcutaneous
How does modest weight gain differ in relation to excessive weight gain in regards to adipose tissue?
Modest gain = inc adipocyte size (hypertrophy)
Excessive gain = inc in BOTH size and number (hyperplasia)
What happens to the the body’s TAG content as BMI inc from 20 to 30?
Doubles
What percentage of chylomicrons are TAGS?
85%
Adipocytes secrete hormones that play a role in what?
Appetite control/ weight gain
Inflammation
Insulin resistance
What are the the two hypotheses regarding factors contributing to obesity?
Hypothesis 1: A biologically predetermined “set point” for body weight for most individuals
or
Hypothesis II: A “settling point” that reflects food intake, energy expenditure and other factors
What are the major factors that regulate body weight?
Genetic
Environmental
(lifestyle/behavioral)
Mutations in is thought to produce hyperphagia and massive obesity?
Leptin gene or
leptin receptor
Ultimately, weight gain results from an ________ bewteen ______ and _______.
inbalance, energy intake, energy expenditure
Why is dyslipidimia?
Increase in serum TAGs esp VLDL
metabolic effect due to obesity
Which tissue are affected by obesity?
Liver
Muslce
Adipose
Which atherosclerotic cardiovascular disease risk factors define Metabolic syndrome?
Visceral adiposity (obesity)
Insulin resistance
Low levels of HDLs
A systemic proinflammatory state
What are several key components leading to metabolic syndrome?
Hypertension Dyslipidemia Insulin resistance Chronic inflammation Impaired fibrinolysis procoagulation central obesity (most telling)
What are the indicators of Metabolic Syndrome?
Elevated fasting blood glucose Elevated waist circumference Elevated TAGs Elevated Blood Pressure Reduced HDL cholesterol
Insulin resistance precedes what?
Diabetes type II
What is the correlation between weight gain and insulin resistance?
Strong
How does insulin affect lipogenesis?
Stimulate
How does insulin stimulation effect amino acid uptake?
Increases
How does insulin stimulation effect protein synthesis?
Increases
How does insulin stimulation effect glycogen storage?
Increases
Why do chylomicrons and VLDL’s accumulate with insulin resistance?
Decreased lipoprotein lipase
What is Sibutramine used for?
Managing obesity
- An appetite suppressant
What is Orlistat used for?
Managing obesity
- Gastric and pancreatic lipase inhibitor, inhibits digestion of TAGs and therefore reduces TAG absorption.
What defines an individual as morbidly obese?
BMI > 35
What are two surgical management methods of managing obesity?
Gastric banding
Ileo gastic bypass
What is the difference between gastric banding and ileo gastric bypass?
GB: dec. stomach size -> reduce intake
IGB: dec stomach pouch size -> dec nutrient absorption from intestine
How does the liver maintain constant blood glucose levels during a fast?
Gluconeogensis
In fat cells, TAGs are degraded to fatty acids and glycerol through activation of what enzyme?
Hormone-sensitive lipase
When does hormone-sensitive lipase become activated?
Phosphorylation = activation
What is the purpose behind the usage of ketone bodies in prolonged starving?
Spare protein degradation
What metabolic adjustments occur during prolonged starving?
- Ketone body usage
- Muscle degradation reduction
- Metabolic rate reduction
- Physcial activity reduction
- Kidney performs gluconeogenesis in addition to liver
- Body fat amount det ultimate survival time
How long after a fast has begun are liver glycogen stores depleted?
1 day
What is Marasmus?
Chronic dietary restriction of carbs, lipids, proteins and other nutrients.
Which diseases are Marasmus associated with?
Anorexia nervosa
GI cancer
Chronic illness (i.e. old age)
How does Anorexia Nervosa affect the brain and nerves?
Bad memory, fatigue
What affect does anorexia nervosa have on the heart?
Low blood pressure
Palpitations
What affect does anorexia nervosa have on blood?
Anemia
What effect does Anorexia Nervosa have on muscles?
Weak
Swollen joints
Once free fatty acids are released from fat cells, what are they used for in the liver?
B-oxidation and Ketone body synthesis
During starvation, does the level of free fatty acids in the serum increase?
No. Flatlines.
What happens to the level of ketone bodies during starvation?
levels increase
What is the role of 3-hydroxybutyrate in the liver?
Formed from acetoacetate at high NADH levels. NAH+ also produced along with 3-hydroxybutyrate, and NAD+ allows for more B-oxidation.
What is acetoacetate?
A ketone body
How do extra hepatic tissue use 3-hydroxybutyrate?
Break it down to NADH and acetoacetate.
NADH leads to 2.5 ATP
What energy source does muscle prefer during fasting?
Ketone Bodies b/c no ATP is needed for activation
How is acetoacetate broken down in muscle?
Thiophorase converts succinyl CoA to Succinate, and takes the CoA and makes Acetoacete into Acetoacyl CoA. Acetoacyl CoA becomes 2 Acetyl CoA.
Why can’t the liver use ketone bodies
Liver lacks thiophorase.
What affect does Anorexia have on the kidneys?
Kidney stones
kidney failure
What affect does anorexia have on body fluids?
Low minerals like potassium, magnesium, and sodium
What affect does anorexia have on the intestines?
Constipation
What affect does anorexia have on hormones?
Loss of menstrual cycle
What is Kwashiorkor?
Deficiency of dietary protein (esp essential amino acids)
What are the manifestations of kwashiorkor?
Muscle wasting
stunted growth
Decreased ability to produce digestive enzymes and new intestinal epithelial cells
Edema in legs and abdomen
What causes the edema in patients with Kwashiorkor?
Decreased concentrations of albumin
Besides deficiency of dietary protein, what else can cause Kwashiorkor?
Partial obstruction of upper GI tract
Deficiency of which vitamins cause Macrocytic anemia?
Deficiencies of:
B9
B12
