cholesterol metabolism

rate limiting step

formation of melvalonate

• HMG-CoA reductase

statins

inhibit HMG-CoA reductase

4 phases

1. 3 acetyl CoA→ melvalonate

2. melvalonate→ phosporylated isoprene

3. 6 phosporylated isoprene→ squalene

4. squalene→ cholesterol

number of carbons in melvalonate 

6

number of carbons in phosphorylated isoprene

5 Carbon atoms and 5 CO2

number of carbons in squalene

30

number of carbons in cholesterol

27

requirements for cholesterol synthesis 

• 18 acetyl CoA

• 36 ATP

• 16 NADPH

effect of glucagon in HMG-CoA

induces phosphorylation inhibiting the enzyme

• it is inhibited because energy needs to be saved for essential processes

when does the liver inhibits the production of cholesterol

1. low ATP

2. When acetyl-CoA is needed for ketone bodies

3. NADPH is needed for antioxidants

effect of insulin on HMG-CoA

dephosphorylates the enzyme activating it

how is cholesterol exportes as

1. bile acids

2. biliary cholesterol

3. cholesteryl esters

when do we export cholesterol as cholesterol esters?

when other organs need cholesterol

bile acid fucntion

emulsification of fats

fucntion of cholesterol esters

for transport or storage

where are bile acids produced

liver

where are bile acids stored

gallbladder

lipoprotein strcuture

hydrophillic outside and hydrophobic inside

chylomicron lipoprotein fucntion

Chylomicrons transport dietary triglycerides and cholesterol from the intestine to peripheral tissues and return chylomicron remnants to the liver.

Name one vitamin derived from cholesterol

Vitamin D

SOURCES of cholesterol

1. diet

2. de novo synthesis in the liver

Exogenous cycle

 handles dietary lipids

1. Lipids enter intestine → enterocytes pack them into chylomicrons → lipoprotein lipase → breaks triglycerides in chylomicrons into free fatty acids → taken up by muscle or adipocytes 

   1. chylomicron remnants travel to liver → taken up & broken down

   2. some cholesterol may be secreted into bile or reused

Endogenous cycle

Lipids synthesized by liver

1. Liver synthesizes VLDL carrying triglycerides & cholesterol to tissues → as triglycerides delivered to tissues VLDL broken down into IDL by lipoprotein lipase & then eventually LDL (rich in cholesterol & will deliver to cells) 

   1. LDL binds to LDL receptors on extrahepatic cells →  they take up cholesterol

   2. LDL can also be taken up by ‘scavenger cells’ → if uncontrolled can lead to atherosclerosis 

      1. HDL collects excess cholesterol and extracellular cholesterol (to prevent accumulation) & brings it to the liver for recycling or excretion 

cholesterol uptake 

Via clathrin-mediated endocytosis