Session 4 Flashcards
Describe, in outline, the reactions involved in glycogen synthesis and breakdown
Glycogenesis:
- Glucose + ATP –> glucose-6-P + ADP (hexokinase in muscle, glucokinase in liver)
- Glucose-6-P glucose-1-P (phosphoglucomutase)
- Glucose-1-P + UTP + H2O –> UDP-glucose + 2Pi
- Glycogen (n residues) + UDP-glucose –> glycogen (n+1 residues) + UDP (glycogen synthase for a1-4, branching enzyme for a1-6)
Glycogenolysis:
Skeletal muscle in response to exercise
Liver in response to fasting/stress
1. Glycogen (n residues) + Pi –> glucose-1-P + glycogen (n-1 residues) (glycogen phosphorylase attacks a1-4, debranching enzyme produces free glucose)
2. Glucose-1-P glucose-6-P (phosphoglucomutase)
3. Glucose-6-P + H2O –> glucose + Pi (glucose-6-phosphotase)
Describe the major energy stores in a 70kg man
TAGs - 600000kJ, 15kg
Glycogen - 4000kJ, 0.4kg
Muscle protein - 100000kJ, 6kg
Compare the function of liver and muscle glycogen
Liver:
Glucose-6-P –> Glucose (glucose-6-phosphatase is present)
Glucose travels in blood so energy is provided for all tissue
Muscle:
Glucose-6-P enters glycolysis and provides energy for respiring muscle (glucose-6-phosphatase is absent in muscle)
Explain the clinical consequences of glycogen storage diseases
Tissue damage (excess storage) Fasting hypoglycaemia Poor exercise tolerance Abnormal glycogen structure Affected liver and/or muscle
Explain why and how glucose is produced from non-carbohydrate sources
Gluconeogenesis:
>8-10h fasting
Occurs in liver and kidney cortex
Pyruvate, lactate, glycerol, galactose, fructose –> glucose
Essential and non essential amino acids –> glucose
NOT acetyl CoA or fatty acids as PDH is irreversible
Key enzymes: fructose 1,6-bis phosphatase, PEPCK
Regulation in response to starvation, prolonged exercise, stress:
Glucagon/cortisol = increased PEPCK+fructose 1,6-bisphosphatase (activates gluconeogenesis)
Insulin = decreased PEPCK+fructose 1,6-bisphosphatase (inhibits gluconeogenesis)
Explain why triacylglycerols are processed for storage
Hydrophobic
Stored in anhydrous, compact form
Stored in specialised adipose tissue
Highly efficient energy store
Utilised in prolonged exercise, stress, starvation, later stage of pregnancy
Storage/mobilisation under hormonal control
Describe how fatty acid degradation differs from fatty acid synthesis
Fatty acid degradation: Cycle of reactions that remove C2 C2 atoms removed as acetyl CoA Produces acetyl CoA Occurs in mitochondria Enzymes separate in mitochondrial matrix Oxidative - produces NADH and FAD2H Requires small amount of ATO to activate fatty acid Intermediates are linked to acetyl CoA Regulated indirectly by availability of fatty acids in mitochondria Stimulated no glucagon and adrenaline Inhibited by insulin Fatty acid synthesis: Cycle of reactions that add C2 C2 atoms added as malonyl CoA Consumes acetyl CoA Occurs in cytoplasm Multi enzyme complex in cytoplasm Reductive - requires NADPH Requires large amounts of ATP Intermediates are linked to fatty acid synthase by carrier protein Regulated directly by activity of acetyl CoA carboxylase Inhibited by glucagon and adrenaline Stimulated by insulin
What is the advantage of having totally or partially different routes for seemingly opposite pathways?
Greater flexibility (different substrates and intermediates) Better control (controlled independently or co-ordinately) Thermodynamically irreversible steps are by-passed
Describe how amino acids are catabolised in the body
Removal of NH2 –> converted to urea –> excreted in urine
Transamination - transfer to keto acid
Amino acid + a-ketoglutarate glutamate + keto acid
Amino acid + oxaloacetate aspartate + keto acid
Enzymes (liver function test):
Alanine aminotransferase (ALT) = alanine –> glutamate
Aspartate aminotransferase (AST) = glutamate –> aspartate
Deamination - disposal of amine gp
Amino acid –> amine gp –> ammonia –> ammonium ion –> urea or glutamine
Amino acids that produce acetyl CoA are ketogenic
Amino acids that produce other products are glucogenic
Some amino acids are both
What are the essential amino acids?
Essential:
Lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine, methionine
May become essential:
Histidine, Arginine, tyrosine, cysteine
Explain the clinical consequences of a defect in phenylalanine metabolism
Phenylketonuria (PKU) is autosomal recessive affecting the gene on chromosome 12. 1 in 15000. There is excess phenylketones excreted in urine.
Phenylalanine hydroxylase enzyme is deficient or missing so phenylalanine is not converted to tyrosine (noradrenaline, adrenaline, dopamine). It builds up and is converted into phenylpyruvate (phenylketone) which is toxic due to its acidity.
Diagnosis: presence of phenylketone in urine or elevated (>1.0mmol/L) phenylalanine.
Treatment: special diet low in phenylalanine
Untreated: inhibition of brain development –> inhibits pyruvate uptake in mitochondria, interferes with energy metabolism
Homocystinuria is autosomal recessive affecting the gene on chromosome 21. 1 in 344000. There is excess homocystine excreted in urine. CBS enzyme is deficient or missing so homocysteine cannot be converted to cystathionine which in turn can’t be converted to cysteine. Homocysteine is converted to methionine using vit b12.
Causes: disorders of connective tissue, muscle, CNS, cardiovascular system.
Similar to Marfan’s syndrome as protein structure is disrupted
Explain the clinical relevance of measuring creatinine in blood and urine
Creatinine –> breakdown of product of creatine
Produced at a constant rate unless muscle is wasting
Excreted via kidneys
Creatinine excretion over 24h is proportional to muscle mass
[creatinine] in urine = marker of urine dilution
Calculate how kidney is functioning
Describe how ammonia is metabolised in the body
- Synthesis of glutamine (glutamate + ammonia using glutamine synthetase) - required ATP
- Excess released, transported to liver or kidney (glutamine hydrolysed by glutaminase to ammonia)
- Ammonia used to make urea in liver or excreted directly in urine in kidney
Hyperammonaemia –> blurred vision, tremors, slurred speech, vomiting, coma, death
Ammonia removes a-ketoglutarate from Kreb’s cycle therefore slows cycle and disrupts energy to brain, is alkaline and affects neurotransmitter synthesis (CNS very sensitive)
Explain the main features of the urea cycle
Occurs in liver
Involves 5 enzymes
Ammonia (toxic) becomes urea (non-toxic)
What is Re-feeding syndrome and how can it be avoided?
When starving people have a diet low in food and protein, enzymes are lost. They have an emaciated appearance.
If they are given too much food or protein, the person may die from ammonia toxicity.
This can be reduced by introducing food to starving people slowly and safely
