Lipid synthesis and Transport

Question 1

What is a Storage of fuel?

Answer 1

• energy providing foods consumed in quantities greater than needed at the time
• fuel is stored
• Carbohydrate stored as glycogen
• store is limited
• long term reserve is lipid (fat) as Triacylglycerol (TAG)

Question 2

Where is TAG in fed state?

Answer 2

Question 3

Fatty acid synthesis in the fed state?

Answer 3

from acetyl Co A
Stimulated by insulin in the fed state

Question 4

What is the first step in FA synthesis?

Answer 4

acetyl CoA to malonyl CoA catalysed by acetyl CoA carboxylase

This is the rate limiting step
Malonyl CoA signifies the fed state. The enzyme is activated by insulin.
Malonyl CoA inhibits carnitine transferase and so inhibits the entry of the FA into the mitochondrion and subsequent oxidation

Question 5

How is NADPH used?

Answer 5

NADPH is needed for fatty acid synthesis. provided by the hexose monophosphate shunt

Question 6

Describe TAG synthesis?

Answer 6

glycerol phosphate +3 fatty acids

Question 7

Describe LIPOPROTEIN STRUCTURE?

Answer 7

inner core
triglycerides & cholesterol esters
outer shell
single layer of phospholipids & cholesterol
& apoproteins

Question 8

Describe Lipoproteins?

Answer 8

• Lipid is insoluble in water
• needs to be transported as a lipid-protein complex

Question 9

Describe the role of apoproteins?

Answer 9

Apoproteins:
* structural role
* recognised by receptors
* activate certain enzymes in lipid metabolism

Question 10

What is the classes of lipoproteins?

Answer 10

• Chylomicrons
  – largest and of lowest density carry mainly dietary TAG
• Very Low Density Lipoprotein (VLDL)
  – carries mainly endogenous TAG
• Low Density Lipoprotein (LDL)
  – carries mainly cholesterol to the tissues
• High Density Lipoprotein (HDL)
  – carries mainly cholesterol from the tissues to the liver

Question 11

Describe the Cholesterol synthesis?

Answer 11

Question 12

Role of LDL receptors?

Answer 12

LDL receptors are very important

• recognise B-100
• remove LDL from the circulation
• (receptor mediated endocytosis)
• deficiency of LDL receptors
• (familial hypercholesterolaemia)
• very high blood cholesterol levels
• premature death from atherosclerosis

Question 13

What is Hyperlipidaemias?
What is it casued by?

Answer 13

Hyperlipidaemia means a high level of cholesterol or triglycerides in your blood and usually occurs when you are overweight of have an unhealthy diet.

• Hypercholesterolaemia
• Hypertriglyceridaemia
• Genetic disposition
• Environment (diet,lifestyle)

Question 14

Examples of genetic Hyperlipoproteinaemias?

Answer 14

• Defective LDL receptor - Hypercholesterolaemia High LDL in blood
• Lipoprotein lipase deficiency - High Chylomicrons and VLDL
• Deficiency of C-II - High chylomicrons and VLDL
• Deficiency of apoproteins involved in remnant uptake - High chylomicron and VLDL remnant

Question 15

Risk factors for Secondary hyperlipoproteinaemias

Answer 15

• Obesity
• Diabetes mellitus type 2
• dietary cholesterol ?
• dietary fatty acid SFA V PUFA
  – n-6 PUFA lower cholesterol
  – n-3 lower TAG
• alcoholism

Question 16

What is Lipoprotein?

Answer 16

• Lp(a) in plasma in high conc associated with increased risk of CHD
• LDL plus apoprotein a
• Levels genetic but can be increased by trans fats and decreased by oestrogen
• Related to plasminogen (target fibrin)
• Slows breakdown of blood clots by competing with plasminogen?

Question 17

What si Atherosclerosis?

Answer 17

Plaque
* complex structure involving inflammation and
proliferation of smooth muscle in artery wall
* contains connective tissue and pool of cholesterol rich lipid
* starts as fatty streak from accumulation of foam cells
* foam cells are macrophages filled with lipid, mainly cholesterol

Question 18

What is the difference between normal LDL

Answer 18

Modified (oxidised) LDL is not recognised by the normal receptor but is taken up by scavenger receptors in foam cells. These receptors are not down regulated and the result is accumulation of cholesterol