Energy storage- glycogen and fat

Question 1

what tissues have an absolute requirement for glucose?

Answer 1

Red blood cells
Neutrophils
Innermost cells of kidney medulla
Lens of the eye

Question 2

What are the consequences of reduced blood glucose? give examples of the measurement

Answer 2

2. 8 mmol/L = confusion
3. 7 mmol/L = weakness, nausea
4. 1 mmol/L = muscle cramps
5. 6 mmol/L = Brain damage/Death

Question 3

how is glycogen stored? What are the body’s main stores of glycogen?

Answer 3

Glycogen is stored as granules

Muscle glycogen (300g) - intra/intermyofibrillar glycogen, can only be used by muscle for contraction

Liver glycogen (100g) - can be used to replenish plasma glucose levels, stored in hepatocytes

Question 4

Describe the structure of glycogen

Answer 4

Polymer - chains of glucose monomers
Branching organised like branches of a tree - originate from a dimer of protein GLYCOGENIN
straight - alpha 1-4 glycosidic bonds
Branched - alpha 1-6 glycosidic bonds (every 8-10 residues)

Question 5

Outline the 4 stages of glycogenesis

Answer 5

1) glucose + ATP —> glucose-6-phosphate + ADP (hexokinase/glucokinase in liver)
2) glucose-6-phosphate —> glucose-1-phosphate (phosphogluco mutase)
3) glucose-1-phosphate + UTP —> UDP-glucose + PPi (G1P uridylyltransferase)

4) glycogen (n residues) + UDP-Glucose —> glycogen (n+1 residues) + UDP
(Glycogen synthase and branching enzyme)

Question 6

Outline the process of glycogenolysis

Answer 6

1) glycogen (n residues) + Pi —> glucose-1-phosphate + glycogen (n-1 residues)
(Glucose phosphorylase or de-branching enzyme)

2) glucose-phosphate —> glucose-6-phosphate (phosphoglucomutase)
3) glucose-6-phosphate used for glycolysis I’m muscle for energy production and to maintain blood plasma concentration by the liver for use by other tissues

Question 7

What enzyme effects the function of glycogen in the muscles and liver?

Answer 7

Glucose-6-phosphatase

Liver: G6P converted to Glucose and exported to blood

Muscle: lacks enzyme and therefore G6P enters glycolysis for energy production for muscle contraction

Question 8

How is liver glycogen metabolism regulated?

Answer 8

Rate limiting enzymes
Synthesis= glycogen synthase
Degradation= glycogen phosphorylase

Glucagon, adrenaline = glycogen synthase = phosphorylation = decrease
glycogen phosphorylase =phosphorylation = increase

Insulin = glycogen synthase = de-phosphorylation= increase
glycogen phosphorylase = de-phosphorylation = decrease

In muscle glucagon = no effect, but AMP acts as allosteric activator of muscle glycogen phosphorylase BUT NOT OF LIVER FORM

Question 9

What are glycogen storage diseases?

Answer 9

Inherited diseases - causing deficiency or dysfunction of enzymes of glycogen metabolism

Severity depends on enzyme/tissue affected

Liver and/or muscle can be affected
Excess glycogen can lead to tissue damage
Diminished glycogen stores can lead to hypoglycaemia and poor exercise tolerance

Question 10

Give 2 examples of glycogen metabolism diseases

Answer 10

Von Gierke’s disease - G6Phosphatase deficiency

Mcardle disease - muscle glycogen phosphorylase deficiency

Question 11

What is the role of gluconeogenesis?

Answer 11

Beyond 8 hours fasting liver glycogen stores will be depleted and a alternative source of glucose is required: gluconeogenesis

Occurs in the liver and lesser extent the kidney cortex

Question 12

What are the 3 pre-cursors for gluconeogenesis?

Answer 12

1) Lactate From anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle)

2) Glycerol Released from adipose tissue
breakdown of triglycerides

3) Amino acids Mainly alanine

Question 13

Why can’t we use acetyl-coA for a net synthesis of glucose?

Answer 13

Would have to feed to TCA cycle

2 carbons in - 2 lost in cycle so not net gain of carbon to produce glucose

Question 14

What are the key enzymes in gluconeogenesis?

Answer 14

1) PEPCK - Phosphoenolpyruvate carboxykinase
2) fructose-1,6-bisphosphatase
3) glucose-6-phosphatase

Question 15

What is the purpose of TAGs?

Answer 15

Energy intake in excess of requirements is converted into TAGs for storage
Hydrophobic- stored in anhydrous form
High efficient energy store
Utilised in prolonged exercise,starvation,pregnancy and stress
Storage and mobilisation is under hormonal control

Question 16

Describe the overview of dietary TAG metabolism

Answer 16

1) fat broken down to fatty acids and glycerol by PANCREATIC LIPASE
2) TAG packaged into Chylomicron to pass through epithelial cells of intestine
3) TAG enters lymphatic system through lacteals and drains into the blood stream at the thoracic duct in the left subclavian vein
4) from here the TAGs can be utilised for fatty acid oxidation for energy or stored in adipose tissue

Question 17

Describe the key features of liver lipogenesis

Answer 17

1) glucose enters glycolysis in the liver cell. Some goes of into the penthouse pathway to produce reducing power in the form of NADPH
2) pyruvate converted to AcetlycoA(2c) and oxaloacetate(4c) which condense together to form citrate which leaves the mitochondria and in the cytosol converted back
3) oxaloacetate —> malate —>pyruvate by malic enzyme provides kore NADPH
4) acetylcoA—>malonlylcoA via acetyl-coA

Inside fatty acid synthase complex, fatty acid chains are grown from NADPH sources ,2 carbons at a time by malonlyl coA (release of co2) to produce TAGs

Question 18

How is lipogenesis controlled?

Answer 18

AcetylcoA carboxylase

Insulin (covalent de-phosphorylation) and citrate (allosteric) increase activity
Glucagon/adrenaline (covalent phosphorylation) & AMP (allosteric) decrease activity

Question 19

How are fats released and mobilised?

Answer 19

Hormone sensitive lipase

Insulin - leads to dephosphorylation and inhibition of HSL

Glucagon and adrenaline - phosphorylation and activation of HSL

Once in blood glycerol travels to liver and utilised as carbon source in gluconeogenesis
Fatty acids travel complexed with albumin to muscle and other tissues for beta oxidation