Lipoprotein Metabolism Flashcards
What is a lipoprotein
Protein-lipid complex
Hydrophobic lipid in core (TG/cholesterol)
Hydrophilic surface
What are triglycerides
Three linked fatty acids
Very hydrophobic
What are the main sources of triglycerides in the blood
Intestine (digested fats)
Liver (send fats to the body)
Uses of cholesterol
lipid constituent of cell membrane (high conc in cytoplasmic membrane)
Precursor of steroid hormones
Precursor of VitD
Precursor of bile acids
What is cholesterol made from
acetate
How to lower cholesterol levels
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
How do statins lower cholesterol
inhibit HMG-CoA reductase
Lipoprotein classification based on density
Chylomicrons (TG)
VLDL (TG)
IDL (CE)
LDL (CE)
HDL (CE)
Chylomicron transport
gut to tissues
VLDL transport
Liver to tissues
HDL transport
Tissues to liver
LDL transport
remaining in circulation
Examples of common genetic defects
-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
Examples of common drugs that exacerbate lipoprotein metabolism problems
Thiazides
B-blockers
corticosteroids
oestrogens
NPC1L1 inhibition
decreased cholesterol uptake
ANGPTL3/ANGPTL3/APOC3 inhibition
increases LPL activity leading to decreased triglyceride rich lipoproteins
CETP inhibition
decreased levels of non-HDL cholesterol
Lp(a) inhibition
decreases Lp(a) production
HMGCR inhibition
decreases endogenous cholesterol biosynthesis and upregulation of LDL receptors leading to increased plasma clearance of LDL
PCSK9 inhibition
decreased degradation of LDL receptors and increased plasma LDL clearance
Statins action
↑ LDL uptake & inhibit HMG CoA reductase
Fibrates action
Stimulates PPAPα, ↑ LPL
prod. ↑LDL uptake, ↓VLDL
prod.
Ezetimibe action
Block absorption of dietary
& biliary cholesterol in
intestine
Resins action
Bind BA’s in intestine - ↑ cholesterol converted to BA
Too much LDL in circulation
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)
What are the risk factors for atherothrombosis
Hyperlipidaemia
Diabetes
Obesity
Hypertension
Genetics
Life style
Homocysteinaemia
Insulin resistance
Age
Gender
Infection
Hypercoagulable states
How to reduce risk of CHD/CAD/CVD
treat:
hypertension
renin angiotensin system
dyslipidaemia
platelet adhesion
hormone replacement/manipulation
What is dyslipidemia
high LDL
low HDL
desirable lipid profile
total <5.2
LDL <2.6
HDL >1.6
TG <1.7
What is hyperlipidemia linked to
atherosclerosis
MI (50% fatal)
diabetes
TG >1.7 mmol/L
