Nutrition, diet, body weight, Energy production I (Carbohydrates & glycolysis) - session 1 Flashcards
metabolism - cell metabolism - metabolic pathways
metabolism= set processes which derive energy +raw materials from food stuffs + use them for repair, growth + activity of tissues of body to sustain life
many reactions - few reaction types- these reactions organised into metabolic pathways which are distinct but integrated
- Some occur in all cells, some only occur in specific cells and others are restricted to compartments within cells
Metabolic pathways have start points, intermediates (metabolites), end points and interconnections between pathways
catabolic pathways and their products
break down of larger molecules to smaller ones (intermediate metabolites) - release large amounts of enerrgy
- → oxidative - release H atoms - ‘reducing power’
products of catabolic metabolism - fuel molecules metabolised to supply:
- building blocks e.g. sugars, AA, cell growth, division + repair
- organic precursors - for interconversion of building block materials e.g. acetyl CoA
- biosynthetic reducing power (NADH, NADPH)
- Energy for cell function - ATP
anabolic pathways
- Synthesise larger important cellular components from intermediate metabolites
- Use energy released from catabolism (ATP)
- Reductive (i.e use H atoms released in catabolism)
energy = capacity to do work
used for..
- biosynthetic work - anabolism - synthesis of cellular components
- transport work - membranes
- maitenance of ion gradients
- nutrient uptake
- specialised funtions
- mechanical work - muscle contraction
- electrical work - nerve impulse conduction
- osmotic work -kidney
humans are isothermal - use chemical bond energy for work
exergonic, endergonic
all cellular activities are expressions of chemical reactions in which chemical bonds broken or formed
characteristic energy change accomponaies each chemical reaction:
- exergonic - release energy
- endergonic - require energy
if free energy change is negative reaction is spontaneous
change in G = DeltaGº + RT.logn ([products]/[reactants]) under non standard conditions
standard conditions: 25oC, 1 atm. pressure, 1M concentration of reactants and products; pH = 7.0
redox reactionss
Oxidation is the removal of electrons or of hydrogen atoms (H+ + e-). A reduction reaction accompanies all oxidation reactions
When fuel molecules are oxidised, electrons and protons are transferred to carrier molecules
- Total conc. of oxidised and reduced carriers is constant
- Therefore, must be cycle between redox processes
- Act as carriers of ‘reducing power’ for
- ATP production (NADH + H+)
- Biosynthesis (NADPH)
H carrier molecules
- Complex molecules- contain components from vitamins (B vitamins
- Converted to reduced formed by adding 2 H atoms (H+ and e-)
- Energy released from food by oxidation – exergonic
How can energy released as reducing equivalents be used to drive energy requiring activities?
- Directly – biosynthesis
- Indirectly, e.g. mitochondrial system to couple NADH to the production of an intermediate ‘energy currency’ molecule = ATP
- Energy released in exergonic reactions used to synthesise ATP
- Part of the free energy conserved as chemical bon energy of terminal phosphate group (PO44-) of ATP
ATP
- When ATP is high- anabolic pathways are activated
- When ATP is low, and ADP and AMP is high- catabolic pathways activated
- Adenylate kinase (myokinase) enzyme converts 2 ADP molecules into 1 ATPand 1 AMP (AMP = low energy signal)
creatine kinase
Creatine kinase made up of 2 subunits, different isoform combinations found in different tissues. CK released from cardiac myocytes) when damaged in MI (heart attack)
- Appears in blood after few hours – diagnostic of MI
breakdown product of creatine and creatine phosphate= creatinine
and key points
- Excreted via kidneys
- Produced by a spontaneous reaction at a constant rate – unless muscle is wasting
- Creatinine excretion proportional to muscle mass => providing measure of muscle mass
- Creatinine conc.in urine = measure of urine dilution
- Can be used to estimate true urinary loss of many substances – e.g. hormones in pregnancy
energy - calories
energy exists in interconvertible forms -cells use chemical energy
- calorie means kilocalorie
- 1kcal= energy needed to raise 1 kg of water by 1 degree Celsius
- 1kcal= 4.2 kilojoules
carbohydrates - 4 kcal per gram
- general formula = (CH2O)n
- Contain aldehyde (-C=OH) or keto (-C=O) group
- multiple -OH groups
- monosaccharide - single sugar units (3-9 C-atoms)
- triose (3), pentose (5), hexose(6) sugars
- disaccharides = 2 units
- oligosaccharides = 3-12 units e.g. dextrins
- polysaccharides= 10-1000’sunits e.g. glycogen, starch, cellulose
proteins - 4kcal per gram
- certain amino acids conditionally essential
- children and pregnant woman = high rate of protein synthesis
- also require some arginine, tyrosine + cyseine in diet
- protein of animal origin considered high quality
- protein of plant origin generally considered lower quality
- most are deficient in 1 or2 essential amino acids
- 9 essential amino acids can’t be synthesised - must be obtained from diet
fats - 9kcal per gram
lipid composed of triacylglycerols - 3 fatty acids esterified to 1 glycerol
- contain much less oxygen than carbs or proteins
- more reduced so yieldsmore energy when oxidised
- required for absorption for fat soluble vitamins (A,D,E & K) from gut
- Provide essential fatty acids – e.g. Linoleic and linolenic acids which can’t be synthesised by body
minerals
- Electrolytes establish ion gradients across membranes + maintain water balance
- Calcium and phosphate essential for structure (bones+ teeth)
- Calcium= important signalling molecule
- Iron = essential component of haemoglobin
- Enzyme co-factors ( iron, magnesium, manganese, cobalt, copper, zinc and molybdenum)
vitamins
- Essential for life
- Required in micro- or milligram quantities
- Fat or water soluble
- Deficiency diseases if inadequate intake
Dietary Reference Values (DRVs)
published by SCAN- are a series of estimates of amount of energy + nutrients needed by groups of healthy UK pop.
- Reference Nutrient Intake (RNI) – used for protein, vitamins, minerals
- Estimated Average Requirement (EAR) – energy
- Lower Reference Nutrient Intake (LRNI) – intakes below this are insufficient for most people
- Safe intake (used when insufficient data)
energy requirements
vary based on age, sex, body composition and physical activity, energy expenditure is the sum of:
- basal metabolic rate – BMR
- Diet induced thermogenesis – DIT – energy required to process food
- Physical activity level – PA
voluntary physical activity:
- Energy required depends on intensity and duration
- Reflects energy demands of skeletal, heart and respiratory muscle
obesity and bmi
- Excessive fat accumulation in adipose tissue
- Measured using BMI, results when energy intake exceeds expenditure
- Associated increased risk of developing some cancers, cardiovascular disease and type 2 diabetes
- Metabolites in blood have a normal range- no fixed value- higher or lower than normal range can help indicate nature of problem
Greater proportion of fat in the upper body is associated with insulin resistance, type 2 diabetes, hypertension, stroke, hyperlipidaemia, etc.
malnutrition
Major preventable cause of death in developing world (also occurs in the UK)
- Damage from low energy intake
- Deficiency diseases of other nutrients
- Low protein intake can result in insufficient blood protein synthesis leading to a decrease in plasma oncotic pressure and oedema (as seen in the disease Kwashiorkor).
lactose intolerance
primary lactase deficiency:
- Absence of lactase persistence allele – only occurs in adult
- highest prevalence in northwest Europe
secondary lactase deficiency:
- caused by injury to small intestine
- Gastroenteritis, Coeliac disease, Crohn’s disease and Ulcerative disease
- Occurs both in adults + infants and is generally reversible
- Congenital lactase deficiency: Extremely rare, autosomal recessive defect in lactase gene – can’t digest breast milk
STAGE 1: Breakdown to building blocks
saliva contains amylase- breaks down starch/ glycogen to dextrins
pancreatic amylase breaks down stugars to monosaccharides
in SI, disaccharides attach to brush border membranes of epithelial cells where broken down by specific enzymes i.e. lactase, sucrase, pancreatic amylase (alpha 1-4 bonds) and isomaltase (a 1-6 bonds).
STAGE 1: Breakdown to building blocks (2)
absorption of monosaccharides
- Active transport by sodium-dependent glucose transporter (SGLT1) into intestinal epithelial + then into the blood supply via GLUT2
- Movement from the blood into cells is through facilitated diffusion via transport proteins (GLUT1-GLUT5)
- Blood glucose concentration is regulated and maintained at around 5mM
STAGE 2: Breakdown to metabolic Intermediates (1)
PHASE 1 of Glycolysis
Phosphorylation of glucose makes it negatively charged making it more reactive + prevents it moving back out of the cell membrane
- Uses 2 moles of ATP per molecule of glucose
- Reactions 1 and 3 are irreversible:
- Reaction 1 enzyme: Hexokinase (glucokinase in liver) converts glucose to glucose-6-phosphate
- Reaction 3 enzyme: Phosphofructokinase-1 converts fructose-6-P to fructose 1,6-bis-P
STAGE 2: Breakdown to metabolic Intermediates (3)
PHASE 2 of Glycolysis and its regulation
Rate of glycolysis up to 200x faster, it can be measured by measuring uptake of FDG
Phosphofructokinase is the main regulator in glycolysis. It is regulated:
- Allosterically- inhibited by high ATP +stimulated by high AMP
- Hormonal- stimulated by insulin and inhibiting by glucagon
STAGE 2: Breakdown to metabolic Intermediates (4)
intermediates
1,3-bis phosphoglycerate can be converted into 2,3- BPG by Bisphosphoglycerate mutase. It is produced in red blood cells and is a regulator of haemoglobin affinity.
see image for intermediates
STAGE 2: Breakdown to metabolic Intermediates (5)
Redox – step 6:
- 2 moles of NADH produced per mole of glucose- pathway requires NAD+
- Total NAD+ and NADH in cell = constant- therefore glycolysis would stop when all NAD+ converted to NADH
- Normally NAD+ regenerated from NADH in stage 4 of metabolism
But
RBC have no stage 3 or 4 of metabolism- stage 4 needs O2 – supply of O2 to muscles + gut often reduced
- need to regenerate NAD+ by some other route
pentose phosphate pathway
Starts from Glucose-6-phosphate, Important source of NADPH required for:
- Reducing power for biosynthesis
- Maintenance of GSH levels
- Detoxification reactions
Produces C5-sugar ribose required for synthesis of:
- nucleotides →DNA & RNA
- No ATP synthesised. CO2 produced
Rate limiting enzyme is Glucose 6-phosphate dehydrogenase
fructose metabolism
- Fructose is a fruit monosaccharide
- Glucose-fructose disaccharide = sucrose
- Metabolised in liver in human
- essential fructosuria = Fructokinase missing -> fructose in urine
- fructose intolerance = aldolase missing
- Fructose-1-P accumulates in liver -> liver damage
- -> treated by removing fructose from diet
galactose metabolism
see image
