carbohydrate metabolism

Question 1

what is the critical blood glucose level?

Answer 1

2.5mM

Question 2

Hypoglycaemia

Answer 2

• Muscle weakness
• Loss of coordination
• Mental confusion
• Sweating Hypoglycaemic coma and death

Question 3

Hyperglycaemia

Answer 3

• Non enzymatic modification of proteins
○ Cataracts
○ Lipoproteins important in atherosclerosis
• Hyperosmolar coma

Question 4

Excess blood glucose

Answer 4

• Glycogen synthesis

* Pentose phosphate synthesis Fatty acid synthesis

Question 5

Lack of blood glucose

Answer 5

• Glycogen breakdown

* Gluconeogenisis

Question 6

Liver

Answer 6

• Main storage of excess glucose
• Glucose phosphorylated by glucokinase and traps glucose in the cell
• Excess glucose is synthesised into glycogen which is branched and compact. Glucose itself is too osmotically active causing an osmotic effect that draw in water and damages the cell.

Question 7

Glycogen synthesis

Answer 7

• G6P converted to Glucose 1 phosphate by phosphoglucomutase
• G1P activated by UTP forming UDP-glucose
• UDP glucose binds to glycogenin to start glycogen synthesis Alpha 1-6 bonds formed at the 11th residue

Question 8

Why glycogen?

Answer 8

• Cannot store glucose as its osmotically driven
• 400mM glucose is stored as 0.01 mM glycogen
• Fats can’t be mobilised as readily
• Fat cannot be used as an energy source in the absence of oxygen Fats cannot be converted in to glucose

Question 9

Glycogen breakdown

Answer 9

• Two products formed
○ Glucose 1 phosphate and glucose
○ Glucose 1 phosphate is the major product
○ Glycogen phosphorylase:
§ Breaks 1-4 links
§ Key enzyme in glycogenolysis and its activity forms glucose-1-phosphate
§ Large, multi-subunit enzyme
§ Many phosphorylase molecules are bound to each glycogen particle:
□ Therefore glycogenolysis can be switched on rapidly
§ G6P ultimately formed provides fuel for working muscles
§ In liver, G6P is de-phosphorylated and secreted into the blood, maintaining 5 mmol/l blood sugar
§ An allosteric enzyme which is activated by phosphorylation but modulated by other factors
○ Translocase:
§ Debranching enzyme has two activities associated with it
□ Transferase activity moves the last glucose residues to the non-reducing end of the existing chain Glucosidase that removes the 1-6 link releasing glucose

Question 10

How is glycogen phosphorylase controlled?

Answer 10

• In muscle, glycogen phosphorylase b can be activated by 5’-AMP without being phosphorylated
• 5’-AMP forms when ATP is depleted
• ATP binds to the same site and blocks activation
• G6P also blocks 5’-AMP activation In the liver the activated phosphorylase a is inhibited by glucose

Question 11

Activation of phosphorylase b kinase by Ca2+

Answer 11

• Ca2+ activate phosphorylase b kinase
○ In muscle, mediating glycogenolysis during muscle contraction
○ Max activity with Ca2+ and phosphorylation In liver, α-adrenergic activation stimulates Ca2+ release

Question 12

Reciprocal regulation of glycogen synthesis and degradation

Answer 12

• Glycogen synthase: ○ Activated in times of plenty
○ Activated by ATP and G6P ○ Inactivation by phosphorylation by protein Kinase A
○ Activated by dephosphorylation by protein phosphatase-1
• Glycogen Phosphorylase:
○ Activated when glucose in short supply
○ Inactivated by ATP and G6P ○ Activated by Phosphorylation by phosphorylase b kinase Inactivated by dephosphorylation by protein phosphatase-1

Question 13

Pentose phosphate pathway

Answer 13

• Activated when plenty of glucose present
• Important for generating ribose 5 phosphate
○ Important precursor for component of DNA and RNA and also important for coenzymes the body needs • When excess glucose present:
○ Pathway generates NADPH which is required for fatty acid synthesis Ribose 5 phosphate can be converted back to G6P

Question 14

Gluconeogenesis

Answer 14

• When glucose is produced from non-carb sources at low glucose levels
• Blood glucose maintained as it is the preferred fuel for the brain and only fuel for red blood cells
• Daily requirement 160g, brain needs 120g
• Total body reserves, 210g
• Gluconeogenic pathway converts pyruvate to glucose
• Mostly takes place in the liver and a little in the kidney, however during starvation, kidney production rises to 40%
• 3 most important substrates for gluconeogenesis are the amino acids:
○ Alanine
○ Lactate
○ Glycerol
1. Pyruvate caboxylase which converts pyruvate to oxaloacetic acid which is then converyed into phosphoenol pyruvate by phosphoenol pyruvate carboxykinase.
2. 3 C converted to G6P by fructose biphosphatase which is then converted to glucose by glucose 6 phosphotase
• Glycerol can be used to synthesize glucose from the backbone of fatty acids
• Oxaloacetic acid from pyruvate is generated in the mitochondria whereas pyruvate in the cytosol
○ Pyruvate transported to mitochondria
○ Then converted to oxaloacetate by pyruvate carboxylase which cannot exit the mitochondria Therefore converted to malate which is then transported out back to the cytosol where its converted to oxaloacetate and then phosphoneol pyruvate.