Lipoprotein Metabolism

Question 1

What is a lipoprotein

Answer 1

Protein-lipid complex
Hydrophobic lipid in core (TG/cholesterol)
Hydrophilic surface

Question 2

What are triglycerides

Answer 2

Three linked fatty acids
Very hydrophobic

Question 3

What are the main sources of triglycerides in the blood

Answer 3

Intestine (digested fats)
Liver (send fats to the body)

Question 4

Uses of cholesterol

Answer 4

lipid constituent of cell membrane (high conc in cytoplasmic membrane)
Precursor of steroid hormones
Precursor of VitD
Precursor of bile acids

Question 5

What is cholesterol made from

Answer 5

acetate

Question 6

How to lower cholesterol levels

Answer 6

1) reduce intake of saturated fats/trans fatty acids/cholesterol/sugars
2) increase intake of soluble fibers (oats/legumes) and fish
3) lose weight
4) exercise (aerobic preferred)
5) moderate alcohol intake

Question 7

How do statins lower cholesterol

Answer 7

inhibit HMG-CoA reductase

Question 8

Lipoprotein classification based on density

Answer 8

Chylomicrons (TG)
VLDL (TG)
IDL (CE)
LDL (CE)
HDL (CE)

Question 9

Chylomicron transport

Answer 9

gut to tissues

Question 10

VLDL transport

Answer 10

Liver to tissues

Question 11

HDL transport

Answer 11

Tissues to liver

Question 12

LDL transport

Answer 12

remaining in circulation

Question 13

Examples of common genetic defects

Answer 13

-LDL receptor deficiency (1: 500) autosomal dominant - no LDL uptake
-Over production of apoB100 (1:50) autosomal dominant - more VLDL produced = more LDL made
-mutant apoE (1:5000 autosomal recessive) - cannot take up IDL = more LDL

Question 14

Examples of common drugs that exacerbate lipoprotein metabolism problems

Answer 14

Thiazides
B-blockers
corticosteroids
oestrogens

Question 15

NPC1L1 inhibition

Answer 15

decreased cholesterol uptake

Question 16

ANGPTL3/ANGPTL3/APOC3 inhibition

Answer 16

increases LPL activity leading to decreased triglyceride rich lipoproteins

Question 17

CETP inhibition

Answer 17

decreased levels of non-HDL cholesterol

Question 18

Lp(a) inhibition

Answer 18

decreases Lp(a) production

Question 19

HMGCR inhibition

Answer 19

decreases endogenous cholesterol biosynthesis and upregulation of LDL receptors leading to increased plasma clearance of LDL

Question 20

PCSK9 inhibition

Answer 20

decreased degradation of LDL receptors and increased plasma LDL clearance

Question 21

Statins action

Answer 21

↑ LDL uptake & inhibit HMG CoA reductase

Question 22

Fibrates action

Answer 22

Stimulates PPAPα, ↑ LPL
prod. ↑LDL uptake, ↓VLDL
prod.

Question 23

Ezetimibe action

Answer 23

Block absorption of dietary
& biliary cholesterol in
intestine

Question 24

Resins action

Answer 24

Bind BA’s in intestine - ↑ cholesterol converted to BA

Question 25

Too much LDL in circulation

Answer 25

Grade I - Foam cells Grade II - fatty streak Grade III - extracellular fatty streak Grade IV - Lipid core Grade V - atherosclerotic plaque lipid core embedded in fibrosis Grade VI - complicated atherosclerotic plaque (plaque rupture, thrombosis, haemorrhage)

Question 26

What are the risk factors for atherothrombosis

Answer 26

Hyperlipidaemia Diabetes Obesity Hypertension Genetics Life style Homocysteinaemia Insulin resistance Age Gender Infection Hypercoagulable states

Question 27

How to reduce risk of CHD/CAD/CVD

Answer 27

treat: hypertension renin angiotensin system dyslipidaemia platelet adhesion hormone replacement/manipulation

Question 28

What is dyslipidemia

Answer 28

high LDL low HDL

Question 29

desirable lipid profile

Answer 29

total <5.2 LDL <2.6 HDL >1.6 TG <1.7

Question 31

What is hyperlipidemia linked to

Answer 31

atherosclerosis MI (50% fatal) diabetes TG >1.7 mmol/L