Energy Storage

Question 1

Describe the structure of glycogen

Answer 1

• Glycogen is a polymer consisting of chains of glucose residues
○ Chains are organised like branches originating from a dimer of the protein glycogenin
○ Glucose residues linked by α-1,4 glycosidic bonds with α-1,6 glycosidic bonds forming branch points every 8-10 residues

Question 2

How is glycogen stored as

Answer 2

• Glycogen stored as granules
○ Muscle glycogen stores only supplies muscles with glucose
○ Liver glycogen store used to replenish plasma glucose concentration

Question 3

What tissues require an absolute glucose supply

Answer 3

§ Red blood cells, neutrophils, innermost cells of kidney medulla, lens of eye

Question 4

Outline the steps of glycogenesis

Answer 4

1. Glucose uses ATP and converts to glucose-6-phosphate using hexokinase enzyme (same as glycolysis)
2. Phosphoglucomutase converts glucose-6-phosphate to glucose-1-phosphate
3. Glucose 1-phosphate converts to UDP-glucose
4. UDP-glucose residues added to glycogen through glycogen synthase or branching enzyme

Question 5

Outline the steps of glycogenolysis

Answer 5

1. Glycogen loses a residue which becomes glucose1-phosphate through glycogen phosphorylase or de-branching enzyme
2. Glucose 1-phosphate becomes glucose 6-phosphate through phosphoglucomutase and used in muscles
3. Glucose 6-phosphate converts to glucose by glucose 6-phosphatase in the liver and used around the body

Question 6

How is glycogen metabolism regulated

Answer 6

○ Enzymes are subject to allosteric control - AMP activates muscle phosphorylase
§ Control by covalent modification
○ Insulin stimulates glycogen synthase and inhibits glycogen phosphorylase
○ Glucagon and adrenaline stimulate glycogen phosphorylase and inhibits glycogen synthase
• In muscles, glycogen stores unaffected by glucagon
○ AMP is an allosteric activator of muscle glycogen phosphorylase but doesn’t affect liver

Question 7

Compare roles of liver and muscle glycogen

Answer 7

• Muscles lack glucose-6-phosphatase meaning it cannot form glucose and therefore stores are only used in muscles
• In liver, G6P converted to glucose and exported to blood

Question 8

Discuss glycogen storage diseases

Answer 8

• Excess glycogen storage can lead to tissue damage
• Diminished glycogen stores can lead to hypoglycaemia and poor exercise tolerance
• Glycogen structure may be abnormal
• Usually liver and/or muscle are affected
• Von Gierke’s disease - can’t release energy from glycogen as lacking glucose-6-phosphatase
• McArdle disease - always exhausted as lacking muscle glycogen phosphorylase

Question 9

Where does gluconeogenesis occur

Answer 9

• Occurs in liver and to lesser extent in kidney cortex

Question 10

How can pyruvate be converted to glucose

Answer 10

○ 7 of the 10 pathways of glycolysis are reversible
○ The remaining 3 are by-passed by enzymes
§ Glucose 6-phosphatase and fructose 1,6-bisphosphatase convert molecules to glucose and fructose 1,6-phosphate respectively
§ Pyruvate carboxylase and PEPCK catalyse and driven by ATP and GTP hydrolysis
□ Provides link between TCA cycle and gluconeogenesis - enables products of amino acid catabolism that are intermediates to TCA cycle to be used for glucose synthesis

Question 11

What precursor molecules can be used to synthesise glucose

Answer 11

○ Lactate - Cori cycle allows recycling of glucose in muscles
○ Glycerol - released from adipose tissue in breakdown of triglycerides
○ Amino acids - mainly alanine
○ Pyruvate

Question 12

How is gluconeogenesis regulated

Answer 12

○ Key enzymes are fructose 1,6-bisphosphatase and PEPCK
○ Regulated in response to starvation, prolonged exercise, stress
○ Glucagon and cortisol stimulates enzymes
○ Insulin inhibits enzymes

Question 13

Through what type of receptors do insulin, glucagon and cortisol act through

Answer 13

• Insulin acts through tyrosine kinase receptor
• Glucagon acts through GPCR
• Cortisol acts through steroid/hormone nuclear receptors

Question 14

Explain why triacylglycerols are an efficient energy store

Answer 14

• TAG highly dense store, high efficiency as high energy per gram
• Stored as bulk in adipose tissue as hydrophobic
• Utilised in prolonged exercise, stress, starvation and during pregnancy

Question 15

Outline the process of lipogenesis

Answer 15

○ Mainly in liver, dietary glucose as major source of carbon (eg, sugar)
○ Glucose undergoes glycolysis to form pyruvate in cytoplasm
○ Pyruvate enters mitochondria and becomes acetyl CoA and oxaloacetate which then condenses into citrate
○ Citrate moves into cytoplasm broken down back into oxaloacetate and acetyl CoA
○ Oxaloacetate converted to malate and back to pyruvate, producing NADPH
§ NADPH important in producing reducing power in anabolic processes (in fatty acid synthase complex)
○ Acetyl CoA converted to malonyl CoA using acetyl CoA carboxylase and ATP
○ Fatty acid synthase complex - malonyl CoA acts as 2 carbon substrate for growing fatty acid chain in fatty acid synthase complex
§ Requires ATP and NADPH
○ Fatty acids combine with glycerol to form triacylglycerol
○ Leaves liver cell as very low density lipoproteins (VLDL)

Question 16

How is lipogenesis controlled

Answer 16

• Acetyl CoA carboxylase acts as major regulator
○ Insulin and citrate increase activity
○ Glucagon/adrenaline and AMP decrease activity

Question 17

Compare fatty acid oxidation and fatty acid synthesis

Answer 17

• Fatty acid oxidation is cycle that removes C2, fatty acid synthesis adds C2
• FAO C2 atoms removed as acetyl CoA, FOS atoms added as malonyl CoA
• FAO produces acetyl CoA, FOS consumes acetyl CoA
• FAO occurs in mitochondria, FOS occurs in cytoplasm
• FAO produces NADH and FAD2H, FOS requires NADPH
• FAO requires small amount of ATP, FAS requires large amount of ATP
• FAO stimulated by glucagon and inhibited by insulin, FAS stimulated by insulin and inhibited by glucagon