Glucose Metabolism

Question 1

What is and what is the point of gluconeogenesis and glycogenolysis

Answer 1

1. Gluconeogenesis is the synthesis of glucose from precursors such as pyruvate, amino acids, lactate, glycerol and citric cycle intermediates (oxaloacetate, aKG)
2. Gluconeogenesis maintains blood glucose levels, which is the primary fuel for the brain and red blood cells, preventing hypoglycaemia (below 2.5mM glucose is fatal)
3. Glycogenolysis is the breakdown of glycogen stimulated via stress-induced adrenaline release or by glucagon when blood glucose level is low, replenishing glucose levels

Question 2

When is gluconeogenesis and glycogenolysis highest and lowest

Answer 2

1. Gluconeogenesis occurs when blood sugar gets low, so occurring after some time has passed after a meal and during the night
2. Glycogenolysis also occurs when blood sugar gets low yet it yields more blood glucose than gluconeogenesis

Question 3

Contrast gluconeogenesis and glycogenolysis

Answer 3

1. Gluconeogenesis is a slower process than glycogenolysis and thus serves to maintain blood glucose levels during longer time periods such as fasting, or periods of long energy demand
2. Primarily occurs in the liver, and a little bit in the kidneys
3. Body reliant on gluconeogenesis when glycogen stores are depleted
4. Glycogenolysis is a rapid process occurring in the liver and muscles
5. Good for short periods where energy demand is high
6. Intense exercise would utilise the glycogenolysis pathway

Question 4

How is glucose homeostasis maintained by hormones

Answer 4

1. The anabolic hormone insulin promotes glycogenesis
2. The catabolic hormones such as glucagon, cortisol, catecholamines (adrenaline hormone, noradrenaline neurotransmitter/hormone), growth hormone

Question 5

How is insulin synthesised

Answer 5

1. Insulin is composed of an A chain (21aa) and B chain (30aa)
2. Peproinsulin is synthesised in ribosomes of pancreatic beta cells containing A chain, B chain, signal peptide and C peptide
3. Peproinsulin is directed to and translocated into the ER where 2 disulphide bridges form between A and B chains, and the signal peptide is removed. This forms proinsulin
4. The folded proinsulin is transported to Golgi where the C peptide is cleaved resulting in mature insulin and C peptide fragments
5. Insulin packaged into secretory vesicles and released into bloodstream when increased glucose levels detected

Question 6

Pretty deeply explain how insulin secretion is regulated

Answer 6

1. Higher concentrations of glucose causes more entering B-cell via GLUT-2 membrane transporter protein
2. Glucose is phosphorylated by glucokinase
3. ATP/ADP ratio increases
4. ATP sensitive K+ channels shut in B-cell plasma membrane
5. Triggers voltage gated Ca2+ channels to open
6. Ca2+ influx triggers exocytosis of insulin containing vesicles

Question 7

Glucagon’s antagonistic effects

Answer 7

1. Promotes catabolism of liver glycogen and adipose tissue triglycerides
2. Stimulates hepatic gluconeogenesis
3. Inhibits protein and lipid synthesis (insulin suppresses catabolism + increase protein synthesis)
4. There is no receptor in muscle for glucagon, only adrenaline can cause glycogenolysis in muscle