Lipid Metab -1b Flashcards
Cholesterol is the precursor of:
vit D (skin) Bile acids (liver) Steroid hormones (adrenals and glands)
Important component of membranes and outer layer of lipoproteins
Cholesterol
Protects gallbladder membrane from harmful effects of bile salts
Cholesterol
Organ that have the greatest capacity to synthesize cholesterol
Iiver Intestine Adrenal cortex Gonads Placenta
All carbon atoms of cholesterol are derived from
Acetyl-CoA
Cholesterol synthesis takes place in the ——–
Cytosol and ER
700mg/day
How many ATPs do you need to synthesize cholesterol?
18 ATP/cholesterol
Five steps in the synthesis of cholesterol
- Biosynthesis of mevalonate (rate-limiting)
- Formation of isoprenoid units/ isopentenyl pyrophosphate
- Formation of squalene
- Cyclization of squalene to lanosterol
- Conversion of lanosterol to cholesterol
Rate limiting step in the synthesis of cholesterol
- Biosynthesis/formation of MEVALONATE
Committed enzyme in the rate limiting step in synthesis of cholesterol
HMG-CoA reductase
An intrinsic membrane protein of the ER and its active site extnds to the cytosol
HMG-CoA reductase
Hormone that Stimulates HMG-CoA reductase
Insulin
Hormone that Inhibits HMG-CoA reductase
Glucagon
Cholesterol inhibits HMG-CoA reductase by what mechanism?
Feedback inhibition
Drugs that inhibit HMG-CoA reductase
“Statins”
Sequential phosphorylation of mevalonate by kinases utilizing ATP;
Takes place several times; most expensive
Step 2 of cholesterol synthesis
Formation of isoprenoid units/isopentenyl phosphate
How many isoprenoid units does it take to make 1 cholesterol?
6 isoprenoid units
1 mevalonate to 1 isop unit = ? ATP
3 ATPs
6 isoprenoid units to 1 cholesterol = ? ATP
18 ATPs
Involves initial ismoerization & then condensation of isopentenyl pyrophosphate (c-5)
Step 3 of cholesterol synthesis
Formation of squalene