Glycogen And Fat

Question 1

Glycogen Stores

Answer 1

Muscle glycogen

• as intra- and intermyofibrillar glycogen granules
• only converted back to glucose-6-phosphate - used by muscle for local energy production

Liver glycogen (up to 10% liver mass)

• glycogen storage granules within hepatocytes
• converted back to glucose and released into the blood for use in other tissues

Question 2

Glycogen structure

Answer 2

Branched - can be broken down and utilised quickly
- alpha 1,6 glycosidic bonds form branch points (branching enzyme)
- alpha 1,4 glycosidic bonds join chains (glycogen synthase)
Has minimal osmotic effect on the cell

Question 3

Glycogenesis

Answer 3

Glucose + ATP —> glucose-6-phosphate + ADP
With hexokinase in the liver

Phosphoglucomutase moves the phosphate from G-6-P to G-1-P

G-1-P + UTP + H2O –> glycogen + UDP

Question 4

Regulation of liver glycogen metabolism

Answer 4

Glycogen synthesis is limited by glycogen synthase
- inhibited by glucagon and adrenaline
- activated by insulin
Glycogen degradation is limited by glycogen phosphorylase
- inhibited by insulin
- activated by glucagon, adrenaline

Glucagon has no effect on muscle glycogen
AMP is an allosteric activator of muscle glycogen phosphorylase

Question 5

Glycogen storage disease

Answer 5

• inherited metabolism disease
• deficiency or dysfunction of enzymes of glycogen metabolise
• 11 distinct types of varying frequency

Liver and/or muscle can be affected
Excess glycogen storage can lead to tissue damage
Diminished glycogen stored can lead to hypoglycaemia and poor exercise tolerance
e.g. Vonnegut Gierke’s disease - Glucose-6-P deficiency and McArdie disease - muscle glycogen phosphorylase deficiency (storage)

Question 6

Gluconeogenesis

Answer 6

• happens after >8hrs after eating
• in the liver and to a lesser extent the kidney cortex
  Precursors
• lactate - from anaerobic glycolysis in exercising muscle and RBC
• glycerol - released from TAC breakdown in adipose
• amino acids - mainly alanine
  NO NET SYNTHESIS OF GLUCOSE FROM ACETYL-COA
  Key enzymes
• PEPCK (oxaloacetate –> phosphophenolpyruvate)
• fructose 1,6-bisphosphate (fructose 1,6-bisphosphate –> fructose-6-phosphate)
• glucose-6-phosphatase (glucose 6-phosphate –> glucose)

Question 7

Regulation of gluconeogenesis

Answer 7

PEPCK and Fructose 1,6-bisphosphatase

• inhibited by insulin
• activated by glucagon and cortisol

Question 8

Glucose utilisation

Answer 8

Glucose from food ~ 2 hours
Glycogenolysis ~ 1 to 10 hours
Gluconeogenesis ~ 8 to 10 hours onwards (with water this can sustain life for up to 40 days)

Question 9

Glucose as the preferred fuel

Answer 9

Some tissues have an absolute requirement for glucose
- erythrocytes (RBC), leukocytes (WBC)
- testes
- kidney medulla
- lens and cornea of the eye
Stable blood glucose is essential for normal brain function. To achieve this a store of glucose - glycogen - is required

Question 10

TAGs utilisation and storage

Answer 10

Hydrophobic - stored in anhydrous form in adipose tissue
Highly efficient energy stores (energy content per gram twice that of carbohydrate or protein)
Used I’m prolonged exercise, stress, starvation and during pregnancy
The storage and utilisation is under hormonal control

Question 11

Adipocytes

Answer 11

Cytoplasm and organelles pushed to the edge of the cells by a large lipid droplet that is mainly composed of TAG and cholesterol esters
~ 0.1 mm in diameter
Can increase in size (hypertrophy) fourfold before dividing and increasing cell number (hyperplasia)

Question 12

TAG metabolism

Answer 12

Pancreas - TAG broken down by pancreatic lipase to fatty acids and glycerol
Transported in blood as a chylomicron
Fatty acid oxidation can only take place in cells with mitochondria and not in the brain since FA do not easily pass the blood-brain barrier

Question 13

Fatty acid synthesis

Answer 13

• mainly occurs in the liver and adipose tissue
• glycolysis in the cytoplasm
• pyruvate enters the mitochondria and forms acetyl-CoA & oxaloacetate
• acetyl-CoA carboxylate produces malonyl-CoA from acetyl-CoA
• fatty acid synthesis complex builds fatty acids by malonyl-CoA (3C - CO2 = 2C addition steps) requires ATP and NADPH

Question 14

Liver lipogenesis

Answer 14

Acetyl-CoA carboxylase

• inhibited by glucagon/adrenaline and AMP
• activated by insulin and citrate

Question 15

Fat mobilisation

lipolysis

Answer 15

Hormone sensitive lipase breaks down TAGs to FA (travels with albumin to muscle and other tissues for beta oxidation) and glycerol (liver source of carbon for gluconeogenesis)

• inhibited by insulin
• stimulated by - glucagon and adrenaline