Carbohydrate Metabolism

Question 1

What are the main symptoms of hypoglycaemia and hyperglycaemia?

Answer 1

Hypoglycaemia:
Muscle weakness
Loss of coordination
Mental confusion
Sweating
Hypoglycaemic coma and death
Hyperglycaemia:
Non-enzymatic modification of proteins as seen in cataracts
Hyperosmolar coma

Question 2

What is glycogenesis?

Answer 2

Glycogen synthesis
Where- Liver (100g), skeletal muscle (300-400g)
When- when blood glucose levels are high
Why- glycogen is a safe way to store glucose
What regulates this- insulin

Question 3

What is glycogen?

Answer 3

Glycogen is a branched polymer of glucose

Question 4

How does glycogenesis occur?

Answer 4

G6P is converted to G1P catalysed by phosphoglucomutase
G1P is converted to UDP-glucose catalysed by UDP-glucose-phosphorylase and uses UTP (uridine triphosphate) and releases PPi
Glycogen is formed from linking glucose molecules through alpha1-4 links and alpha 1-6 links forming branches
Formed on a protein primer called glycogenin
The synthesis is regulated by the enzyme glycogen synthase
The branched points are introduced using the ‘branching enzyme’

Question 5

Why is glucose turned to glycogen specifically?

Answer 5

Cannot store glucose as it is osmotically active
400 mM glucose is stored as 0.01uM glycogen
The branched structure of glycogen means it can be rapidly mobilised

Question 6

What is glycogenolysis?

Answer 6

Glycogen breakdown
Occurs in the liver and muscle
Occurs when glucose levels are low
Stimulated by glucagon, adrenaline, noradrenaline and growth hormone

Question 7

What products does glycogenolysis yield?

Answer 7

Glucose 1-phosphate

Glucose

Question 8

Recall the process of glycogenolysis.

Answer 8

1. Phosphorylate breaks an a1-4 link which forms a G1P molecule
   1b. That molecule gets converted into G6P using phosphoglucomutase
2. Debranching- here transferase moves 3 residues to an existing chain (the main glycogen chain)
3. α-1,6-Glucosidase, also known as the debranching enzyme, hydrolyses the α-1, 6-glycosidic bond, resulting in the release of a free glucose molecule
   3b.The freed glucose from the branched chain is converted to G6P catalysed by hexokinase in muscle
4. Phosphorylase breaks off a glucose molecule attached by 1-4 linkage and this continues corresponding to the needs of the organism
   In the liver (and kidneys), after the G1P is turned to G6P it can then be turned to glucose through G6-phosphatase

Question 9

What is glycogen phosphorylase?

Answer 9

Phosphorylase is a large, multi-subunit enzyme that plays a key role in glycogenolysis
It is regulated by allosteric interactions that signal the energy state of the cell
Also regulated by reversible phosphorylation regulated by hormones such as insulin, glucagon, adrenaline and noradrenaline
Regulation of glycogen phosphorylase differs in muscle and liver

Question 10

How is glycogen phosphorylase controlled?

Answer 10

Phosphorylase is an example of an allosteric enzyme; it is activated by phosphorylation but modulated by other factors
In muscle, glycogen phosphorylase b can be activated by 5’-AMP without being phosphorylated
ATP binds to the same site and blocks activation
Glucose-6-phosphate also blocks 5’-AMP activation
In the liver the activated phosphorylase a is inhibited by glucose
(5’-AMP forms when ATP is depleted)

Question 11

How do hormones regulate glycogenolysis?

Answer 11

Insulin inhibits
Glucagon stimulates in the liver
Adrenaline stimulates in the muscle
Cortisol is a weak stimulus

Question 12

How is phosphorylase b kinase activated by Ca2+?

Answer 12

Ca2+ ions activate phosphorylase b kinase
In muscle, mediating glycogenolysis during muscle contraction; only gets max. activity with Ca2+ and phosphorylation
In the liver a-adrenergic activation stimulates Ca2+ release

Question 13

What is the difference between the regulation of glycogen synthesis vs glycogen degradation?

Answer 13

Synthesis:
Glycogen synthase
Activated in times of plenty
Stimulated by Insulin
Degradation:
Glycogen phosphorylase
Activated the blood glucose is low 
Stimulated by glucagon, adrenaline and noradrenaline

Question 14

What is the pentose phosphate pathway?

Answer 14

The pentose phosphate pathway is a metabolic pathway parallel to glycolysis
It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides

Question 15

What is gluconeogenesis?

Answer 15

New glucose
Gluconeogenic pathway converts pyruvate to glucose
Synthesis is from non-carbohydrate sources- triglycerides, lactate and a small amount in the intestine
When blood levels are low- fasting, starvation
Takes place mostly in the liver and a little in the kidney but during starvation, kidney productions rise to 40%
1.Pyruvate is converted to oxaloacetic acid by the enzyme pyruvate carboxylase
2.Oxaloacetic acid is converted to pyruvate kinase by the enzyme phosphoenolpyruvate carboxykinase
3.F 1,6 P is converted to F6P by the enzyme fructose 1-6 bisphosphatase
4.G6P is converted to glucose by the enzyme glucose 6-phosphatase

Question 16

What happens in the liver during gluconeogenesis?

Answer 16

Gluconeogenesis is usually accompanied by ketogenesis
Three most important substrates for gluconeogenesis are the amino acid (alanine), lactate and glycerol (from TG)
Used to maintain blood glucose as it is the preferred fuel for the brain and the only fuel for RBC
Daily requirement is 160g, the brain needs 120g
Total body reserves are 210g