Session 5: Energy storage and lipid transport

Question 1

Describe major energy stores in a 70kg man

Answer 1

15kg triacylglycerol, 6kg protein, 0.4kg glycogen

Question 2

Describe the reactions involved in glycogen synthesis

Answer 2

Glycogenesis
1. Glucose+ ATP= Glucose 6 phosphate + ADP using HEXOKINASE
2. Glucose 6 phosphate gives glucose 1 phosphate using PHOSPHOGLUCOMUTASE
3. Glucose 1 phosphate + UTP + H20 = UDP-glucose + P using G1P URIDYLYLTRANSFERASE.
4. Glycogen(n) + UDP glucose = Glycogen(n+1) + UDP using GLYCOGEN SYNTHASE or BRANCHING ENZYME depending on where glucose is added to chain.
Note: sythesis of glucose requires energy.

Question 3

Describe reactions involved in glycogen breakdown

Answer 3

Glycogenolysis
1. Glycogen(n) = glucose 1 phosphate + Glycogen(n-1) using GLYCOGEN PHOSPHORYLASE or DE BRANCHING enzyme depending where glucose unit was
2. Glucose 1 phosphate = glucose 6 phosphate using PHOSPHOGLUCOMUTASE. Glucose 6 phosphate can be used in the muscles for energy production through GLYCOLYSIS and glucose is released in the liver for use by other tissues

Question 4

Compare the functions of liver and muscle glycogen

Answer 4

Liver: Glycogen is converted to glucose 1 phosphate, glucose 6 phosphate using glucose 6 phosphatase creates glucose. Liver glycogen is a buffer of blood glucose levels
Muscle: Glycogen is converted to glucose 1 phosphate, glucose 6 phosphate, undergoes glycolysis to produce CO2, ATP, and lactate. Muscle lacks glucose 6 phophatase enzyme. G6P enters glycolysis for energy production.

Question 5

Explain the clinical consequences of glycogen storage diseases

Answer 5

Arise from deficiency or dysfunction of enzymes of glycogen metabolism.Excess glycogen storage can lead to tissue damage. Low glycogen storage leads to hypoglycaemia and poor exercise tolerance. Examples: von Gierke’s disease(glucose 6 phosphate deficiency) and McArdle disease muscle glycogen phosphorylase deficiency)

Question 6

Explain why and how glucose is produced from non-carbohydrate sources. Name the 3 major precursors and enzymes

Answer 6

Beyond 8 hours of fasting, liver glycogen starts to deplete and an alternative source of glucose is needed: gluconeogenesis. Occurs in liver and kidney cortex.
3 major precursors:
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.
Note: Acetyl CoA cannot be converted to pyruvate as pyruvate dehydrogenase reaction is irreversible. So acetyl CoA cannot form glucose. This is why ethanol consumption may lead to hypoglycaemia- it induces insulin secretion.
Key enzymes:
1. PEPCK: production of GDP
2. Fructose 1,6 biphosphatase: production of fructose 6 phosphate
3. Glucose 6 phosphate: production of glucose

Question 7

What is the cory cycle?

Answer 7

Glucose in liver moves to muscle, where it produces 2 lactate, and moves through the blood to the liver. Then this cycle continues and the 2 lactate in the liver produces 2 glucose.

Question 8

Explain the regulation of gluconeogenesis using the enzymes involved

Answer 8

Hormone: Glucagon, cortisol. When PEPCK and fructose 1,6 biphosphatase enzymes have increased activity, gluconeogenesis is stimulated.
Hormone: Insulin
When PEPCK and fructose 1,6, biphosphatase enymes have decreased activity, gluconeogenesis is inhibited.

Question 9

Explain why triacylglycerols can be used as efficient energy storage molecules in adipose tissue

Answer 9

Excess TAG is stored in adipose tissue in anhydrous form. It is a highly efficient energy store as energy content per gram is twice that of carbohydrates or proteins. Its storage and mobilisation is controlled by hormones. Note that fat cells can be created, not destroyed.

Question 10

Describe how triacylglycerols are processed for storage

Answer 10

look at notes for pathway

Question 11

Describe how fatty acid degradation differs from fatty acid synthesis

Answer 11

Degradation vs synthesis
Remove C2 vs add C2
Produces acetyl CoA vs consumes acetyl CoA
Occurs in mitochondria vs occurs in cytoplasm
Oxidative- produces NADH and FAD2H vs reductive-reuires NADPH
Requires small amount of ATP to activate fatty acid vs requires large amount of ATP to drive process
Glucagon and adrenaline stimulate vs inhibit
Insulin inhibits vs insulin stimulates

Question 12

Describe how lipids are transported in the blood

Answer 12

Lipids are hydrophobic molecules insoluble in water, and are therefore transported in blood bound carriers called lipoprotein particles. Some are carried in albumin, which has limited capacity.

Question 13

Explain how tissues obtain lipids they require from lipoproteins

Answer 13

look at pathway on notes

Question 14

What is the typical plasma concentration range of total cholesterol?

Answer 14

Less than 5mmol/L

Question 15

What is the function of apolipoprotein

Answer 15

They can be integral-passing through the phospholipid bilayer or peripheral- resting on top. They package water insoluble lipids and act as a co-factor for enzymes, and as ligands for cell surface receptors.

Question 16

What are the 5 different classes of mature lipoproteins

Answer 16

Chylomicrons, Very low density lipoproteins(VLDL), Immediate density lipoproteins(IDL), low density lipoproteins(LDL), and high density lipoproteins(HDL).

Question 17

What are the functions of the 5 classes of mature lipoproteins

Answer 17

Chylomicrons: transports dietary TAG from the intestine to tissues like adipose tissue.
VLDL: transport of TAG synthesized in liver to adipose tissue for storage
IDL: Short lived precursor of LDL. Transports cholestrol synthesized in liver to tissues
LDL: Transports cholestrol synthesized in liver to tissues
HDL: transports excess tissue cholesterol to liver for disposal as bile salts and to cells requiring more cholestrol

Question 18

Why are LDL particles more suspectible to oxidative damage?

Answer 18

Half life of LDL in blood is much longer than VLDL or IDL making LDL more suspectible to oxidative damage. Oxidised LDL taken up by macrophages transform into foam cells and form atherosclerotic plaques.

Question 19

How does LDL enter cells

Answer 19

Cells that need cholesterol express LDL receptors on plasma membrane. LDL complex taken into cell by endocytosis into endosomes. Fuse with lysosomes for digestion to release cholesterol and fatty acids.

Question 20

Describe the synthesis and fate of HDL particles

Answer 20

Synthesis: New HDL is made by liver and intestine(low TAG levels). HDL particles can also bud off from chylomicrons and VLDL as they are digested by LDL. Free apoA-I(enzyme) can acquire cholesterol from other lipoproteins and cell memebranes to form new HDL
Fate: mature HDL taken up by liver via specific receptors. Cells requiring additional cholesterol ester for steroid hormone synthesis etc can use scavenger receptors to obtain cholestrol from HDL. HDL can also exchange cholesterol ester for TAG via cholesterol exchange transfer protein(CETP)

Question 21

What is hypercholesterolaemia?

Answer 21

High level of cholesterol in body. Leads to yellow patches on eyelids, nodules on tendon,white/blueish circle around eye(common in older peopel, a sign of disease in younger people)

Question 22

What is the treatment for hyperlipoproteinaemias

Answer 22

1. Diet: reduce cholesterol and lipid intake. Increase fibre
2. Lifestyle: increase exercise, stop smoking to reduce cardiovascular risk
3. If no response, use statins. Reduce cholesterol synthesis by inhibiting HMG-CoA reductase enzyme. Eg. Atorvastatin. Therefore, production of cholestrol from acetyl CoA reduces.
4. If not, bind bile salts in GI tract. Forces liver to produce more bile acids using more cholesterol. eg. Colestipol