Energy storage

Question 1

Describe the major energy stores in a 70kg man.

Answer 1

• TAG
  
  • 15kg
    
    • 600,000kJ
• Glycogen
  
  • 0.4kg
    
    • 4,000kJ
• Muscle protein
  
  • 6kg
    
    • 100,000kJ

Question 2

Describe the structure of glycogen

Answer 2

• polymer of chains of glucose residues
  • chains originate from dimer of glycogenin
    • residues linked by α-1,4 glycosidic bonds, with α-1,6 glycosidic bonds forming at branch points every 8-10 residues

Question 3

• Describe the reactions involved in glycogen synthesis

Answer 3

• glucose + ATP → G6P + ADP
  
  • hexokinase (glucokinase in liver) - ACTIVE
• G6P ↔G1P
  
  • phosphoglucomutase
• G1P + UTP + H2O → UDP-glucose + Pi
  
  • G1P uridylyltransferase - ACTIVE
• Glycogen (n residues) + UDP glucose → Glycogen (n+1 residues) + UDP
  
  • glycogen synthase for α-1,4 glycosidic bonds
  • branching enzyme for α-1,6 glycosidic bonds

Question 4

• Describe the reactions involved in glycogen breakdown

Answer 4

• Glycogen (n residues) + Pi → G1P + Glycogen (n-1 residues)
  • glycogen phosphorylase or de-branching enzyme
• G1P ↔G6P
  • phosphoglucomutase

Question 5

Glycogenolysis vs glycogenesis

Answer 5

• not simply reverse
  
  • different enzymes allow for simultaneous inhibition of one pathway, and stimulation of another

Question 6

• Identify the functions of muscle glycogen.

Answer 6

can only be use by muscle for energy production

    - G6P fed into glycolysis

        - lacks glucose-6-phosphatase


- glucagon has no effect

- AMP is allosteric activator of glycogen phosphorylase

    - not in liver form of enzyme

Question 7

Identify the function of liver glycogen

Answer 7

• released by liver into blood for use in other tissues
• G6P converted to glucose
  
  • exported to blood
    
    • buffers blood pH

Question 8

Glycogen synthase

Answer 8

rate limiting of glycogen synthesis

Question 9

Glycogen phosphorylase

Answer 9

rate limiting of glycogen degradation

Question 10

Regulation of liver glycogen metabolism

Answer 10

• Glucagon, adrenaline
  
  • decrease glycogen synthase activity
  • increase glycogen phosphorylase activity
• Insulin
  
  • increase glycogen synthase activity
  • decrease glycogen phosphorylase activity

Question 11

Enzyme mechanism of action with glucagon, adrenaline and insulin

Answer 11

• glucagon, adrenaline
  
  • phosphorylation
• insulin
  
  • de-phosphorylation

Question 12

• Explain the clinical consequences of glycogen storage diseases.

Answer 12

liver and/or muscle affected
- excess glycogen storage = tissue damage
- diminished stores = hypoglycaemia & poor exercise tolerance

Question 13

Glycogen storage disease examples

Answer 13

• von Gierke’s disease: glucose-6-phosphatase deficiency
• McArdle: muscle glycogen phosphorylase deficiency

Question 14

• Explain why glucose is produced from non-carbohydrate sources.

Answer 14

• gluconeogenesis requires after ~ 8-10hrs fasting
  • maintain plasma glucose ~ 5mmol/L
• mostly occurs in liver and lesser extent in kidney cortex

Question 15

• Explain how glucose is produced from non-carbohydrate

Answer 15

• pyruvate, lactate & glycerol → glucose
• essential & non essential amino acids
  • whose metabolism involves pyruvate/intermediates of TCA
    • mostly alanine

Question 16

Why can acetyl coA not be converted to glucose.

Answer 16

• reaction catalysed by PDH is irreversible
• some carbon lost as CO2

Question 17

What are the key enzymes & reactions in gluconeogenesis

Answer 17

• glucose-6-phosphatase
  
  • g6p→glucose
• fructose-1,6-bisphosphatase
  
  • f1,6bp→f6p
• phosphoenolpyruvate carboxykinase (PEPCK)
  
  • oxaloacetate → phosphoenolpyruvate (intermediate of glycolysis)
• pyruvate carboxylase
  
  • pyruvate→oxaloacetate

(all have -ve ∆G)

Question 18

Regulation of gluconeogenesis.

Answer 18

• Glucagon, cortisol
  
  • PEPCK: increased enzyme amount
  • Fructose-1,6-bisphosphatase: increased enzyme amount & activity
    
    • stimulates gluconeogenesis
• Insulin
  
  • vice versa
    
    • inhibits gluconeogenesis

Question 19

Describe the Cori cycle.

Answer 19

• lactate produced in muscle/RBC in anaerobic glycolysis
• trafficked to liver, lactate → glucose (gluconeogenesis)
• glucose exit liver + returned to muscle

Question 20

Explain why triacylglycerols can be used as efficient energy storage molecules in adipose tissue.

Answer 20

energy content per gram is twice that of carbs/protein

Question 21

Adipocytes

Answer 21

• large lipid droplet of mainly TAG & cholesterol ester
• cytoplasm & organelles pushed to edge
• increase in size fourfold on weight gain before dividing to increase total number
  • division is irreversible

Question 22

• Describe how dietary triacylglycerols are processed for storage.

Answer 22

1. TAG → fatty acids + glycerol
   
   • pancreatic lipase
2. Absorbed into intestinal epithelial cells
3. Re-synthesised into TAG & packaged into chylomicron
4. Drain into lymphatic system then enters circulation
5. Storage
   
   • TAG stored in adipose

Question 23

• Describe how dietary triacylglycerols are processed for utilisation.

Answer 23

1. Chylomicrons in circulation enter tissues
2. Fatty acid oxidation to produce energy
   • not cells lacking mitochondria e.g. RBC or brain
     -> fatty acid don’t easily pass through blood-brain barrier

Question 24

• Describe how fatty acid degradation differs from fatty acid
synthesis.

Answer 24

Degradation
- cycle of reactions that remove C2 as acetyl coA
- occurs in mitochondria (separate enzymes)
- oxidative - produce NADH & FAD2H
- requires little ATP
- intermediates linked to coA
- regulated indirectly by fatty acid availability in mitochondria
- glucagon & adrenaline stimulate
- insulin inhibit

Synthesis
- cycle of reactions that add C2 as malonyl coA (consumes acetyl coA
- occurs in cytoplasm (multi-enzyme complex)
- reductive - requires NADPH
- requires lots of ATP
- intermediates linked to fatty acid synthase by carrier protein
- regulated directly by acetyl-coA carboxylase activity
- glucagon & adrenaline inhibit
- insulin stimulates