Energy Storage Flashcards
Describe the structure of glycogen
• 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
How is glycogen stored as
• Glycogen stored as granules
○ Muscle glycogen stores only supplies muscles with glucose
○ Liver glycogen store used to replenish plasma glucose concentration
What tissues require an absolute glucose supply
§ Red blood cells, neutrophils, innermost cells of kidney medulla, lens of eye
Outline the steps of glycogenesis
- Glucose uses ATP and converts to glucose-6-phosphate using hexokinase enzyme (same as glycolysis)
- Phosphoglucomutase converts glucose-6-phosphate to glucose-1-phosphate
- Glucose 1-phosphate converts to UDP-glucose
- UDP-glucose residues added to glycogen through glycogen synthase or branching enzyme
Outline the steps of glycogenolysis
- Glycogen loses a residue which becomes glucose1-phosphate through glycogen phosphorylase or de-branching enzyme
- Glucose 1-phosphate becomes glucose 6-phosphate through phosphoglucomutase and used in muscles
- Glucose 6-phosphate converts to glucose by glucose 6-phosphatase in the liver and used around the body
How is glycogen metabolism regulated
○ 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
Compare roles of liver and muscle glycogen
- 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
Discuss glycogen storage diseases
- 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
Where does gluconeogenesis occur
• Occurs in liver and to lesser extent in kidney cortex
How can pyruvate be converted to glucose
○ 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
What precursor molecules can be used to synthesise glucose
○ Lactate - Cori cycle allows recycling of glucose in muscles
○ Glycerol - released from adipose tissue in breakdown of triglycerides
○ Amino acids - mainly alanine
○ Pyruvate
How is gluconeogenesis regulated
○ 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
Through what type of receptors do insulin, glucagon and cortisol act through
- Insulin acts through tyrosine kinase receptor
- Glucagon acts through GPCR
- Cortisol acts through steroid/hormone nuclear receptors
Explain why triacylglycerols are an efficient energy store
- 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
Outline the process of lipogenesis
○ 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)
