Lipids, lipoproteins and hyperlipidemias

Question 1

What are the 3 functions of lipids?

Answer 1

1. Precursors for steroid hormones
2. Energy source
3. Structural component in cell membrane

Question 2

What are the different types of lipids?

Answer 2

Cholesterol
Fatty acids
Mono, di and triglycerides
Phospholipids
Steroids, prostaglandins and sphingolipids

Question 3

Describe the structure of a triglyceride.

Answer 3

Glycerol backbone and 3 fatty acids

Question 4

What is the major fuel source for lipolysis?

Answer 4

Triglycerides

Question 5

What are the 2 functions of phospholipids?

Answer 5

Part of the membrane bilayer

Fuel source

Question 6

Describe the structure of a phospholipid.

Answer 6

Glycerol backbone with 2 FA tails and a polar (hydrophilic) head group

Question 7

What are the 4 functions of cholesterol that make it important for human life?

Answer 7

1. Cell membrane permeability and fluidity
2. Precursor for steroid hormone synthesis
3. Vitamin D synthesis
4. Manufacture bile salts

Question 8

How do we get cholesterol in the body?

Answer 8

Absorbed through the diet (animal fats) or synthesized in the body

Question 9

How is cholesterol broken down in the body?

Answer 9

Humans cannot breakdown cholesterol - can only be excreted in faeces

Question 10

Where does cholesterol synthesis occur?

Answer 10

90% of cholesterol synthesis occurs in the liver and intestine

Also occurs in the brain, skin, adrenals, gonads

Question 11

What is the rate limiting enzyme in cholesterol synthesis?

Answer 11

HMG-CoA reductase (converts HMG-CoA to mevalonate)

Question 12

What controls cholesterol synthesis?

Answer 12

Cholesterol levels - increased cholesterol inhibits synthesis
Insulin - increases cholesterol synthesis
Glucagon - decreases cholesterol synthesis

Question 13

How are lipids packaged?

Answer 13

In structures called lipoproteins

Question 14

What is the general structure of a lipoprotein?

Answer 14

Lipid core - primarily triglycerides and cholesterol esters with small amounts of sphingolipids and fat soluble vitamins

External layer - hydrophilic layer made of phospholipids, unesterified free cholesterol, and apolipoproteins/apoproteins

Question 15

What are the 4 main types of lipoproteins?

Answer 15

1. Chylomicrons
2. VLDL
3. LDL
4. HDL

Question 16

What is the function of chylomicrons?

Answer 16

Main carrier of dietary triglycerides

Question 17

What is the function of VLDL?

Answer 17

Main carrier of endogenously produced triglycerides

Question 18

What is the function of LDL?

Answer 18

Main carrier of cholesterol

Question 19

What is the function of HDL?

Answer 19

Protective function - carries cholesterol from extrahepatic tissues to liver for excretion

Question 20

Where is VLDL synthesized?

Answer 20

In the liver

Question 21

How is LDL synthesized?

Answer 21

Generated from VLDL

Question 22

Why should you not see chylomicrons in fasting plasma?

Answer 22

Because they are only synthesized by the gut after a meal

Question 23

Structurally what is Lp(a)?

Answer 23

Structurally related to LDL but has a carbohydrate rich protein apo(a)

Question 24

What is the function of Lp(a)?

Answer 24

Functional role not established but it is known to compete with plasminogen for binding sites = may play a role in thrombogenesis (clotting)

Plays a role in atherogenesis - increase levels are associated with increased risk for CHD

Question 25

What are the 4 roles/functions of apoproteins/apolipoproteins?

Answer 25

1. Facilitate lipid solubilisation 2. Help maintain structural integrity of lipoproteins 3. Serve as a ligand for lipoprotein receptors 4. Regulate activity of lipoprotein metabolic enzymes

Question 26

What are the 4 major lipid transport pathways?

Answer 26

1. Exogenous pathway (chylomicrons) 2. Endogenous pathway (VLDL) 3. Intracellular-cholesterol pathway (LDL) 4. Reverse-cholesterol transport pathway (HDL)

Question 27

What are the 3 types of hyperlipidemias?

Answer 27

1. Hypercholesterolemia 2. Hypertriglyceridemia 3. Combined hyperlipidemia

Question 28

What are the causes of hyperlipidemias?

Answer 28

Primary cause - genetic defect Secondary causes - endocrine/metabolic, kidney/liver damage, drugs Often they are a combination of genetic and environmental factors

Question 29

What causes familial hypercholesterolemia?

Answer 29

Defect in LDL receptor - mutations can occur in various parts of the receptor synthesis, transport, binding, clustering and recycling

Question 30

What does familial hypercholesterolemia cause?

Answer 30

Xanthomas - deposition of cholesterol rich material (lumps of cholesterol in the skin)

Question 31

What causes familial hypertriglyceridemia and what does it lead to?

Answer 31

LPL deficiency - causes high serum triglyceride levels due to accumulation of chylomicrons and VLDLs

Question 32

What are the symptoms of familial hypertriglyceridemia?

Answer 32

Manifests in early childhood with repeated episodes of abdominal pain, xanthomas, acute pancreatitis

Question 33

What causes familial combined hyperlipidemia?

Answer 33

Elevated TG or cholesterol or both Causes increased production of ApoB which leads to increased VLDL and LDLs

Question 34

What are some possible causes of secondary hyperlipidemias?

Answer 34

Diabetes/obesity - cause LPL deficiency, overproduction of VLDL by the liver, incomplete VLDL metabolism Hypothyroidism Nephrotic syndrome (kidney disease) Drugs Other eg alcohol, high CHO diet, pregnancy

Question 35

What is polygenic hypercholesterolemia?

Answer 35

Most common cause of elevated serum cholesterol - caused by western life style of a high fat diet on a susceptible genotype - causes downregulation of LDLR

Question 36

What is arteriosclerosis?

Answer 36

Any disease which leads to thickening and hardening of the artery wall (becomes narrowed or even blocked completely)

Question 37

What is atherosclerosis?

Answer 37

Specific type of arteriosclerosis - involves the formation of plaques (fatty tissue accumulation) in the inner (intimal) layer of large and medium sized elastic arteries

Question 38

What is the lipid panel?

Answer 38

Total cholesterol Triglycerides LDL cholesterol HDL cholesterol Results interpreted with medical history to establish risk for developing CHD

Question 39

How do you measure TG and cholesterol?

Answer 39

Coupled enzyme assays which involved linked reactions to form a coloured product

Question 40

How do you measure lipoproteins?

Answer 40

Measured by ultracentrifugation to seperate lipoproteins based on their physical properties - density, size, charge

Question 41

How do you measure chylomicrons?

Answer 41

Standing plasma test - plasma placed in fridge (4c) overnight, chylomicrons accumulate as floating 'cream' layer In fasting plasma chylomicrons are abnormal

Question 42

What are the major risk factors for cardiovascular disease?

Answer 42

``` Hyperlipidemias Obesity Smoking Nutrition Exercise Genetics Hypertension ```

Question 43

What are the therapeutic interventions to reduce plasma/serum lipids?

Answer 43

Dietary changes/exercise - to increse HDL and lower LDL = omega 3 and 6 FA eg fish oils Drugs eg statins - inhibit HMG-CoA reductase to lower LDL cholesterol

Question 44

Explain the exogenous lipid transport pathway.

Answer 44

Check with writing.

Question 45

Explain the endogenous lipid transport pathway.

Answer 45

Check with writing.

Question 46

Explain the intracellular-cholesterol transport pathway.

Answer 46

Check with writing.

Question 47

Explain the reverse cholesterol transport pathway.

Answer 47

Check with writing.

Question 48

Explain the pathophysiology of atherosclerosis.

Answer 48

Check with writing.