Cholesterol Metabolism 1 - CB

Question 1

What form does cholesterol leave the liver?

Answer 1

unmodified free cholesterol in bile, as VLDL, or conversion to bile acids/salts

Question 2

What happens if the balance of cholesterol influx and efflux is off?

Answer 2

it deposits on endothelial linings

Question 3

What is a steroid nucleus?

Answer 3

4 planar rings

Question 4

What is cholesteryl ester?

Answer 4

cholesterol with a FA attached (The form found in blood plasma) it is more hydrophobic

Question 5

What gives cholesterol its polar head?

Answer 5

-OH (hydroxyl) Carbon 3

Question 6

How does cholesterol affect a membrane at physiologic conditions?

Answer 6

increases packing thus increasing rigidity and decreasing permeability and fluidity.

Question 7

What gives cholesterol its hydrophobic part of its amphipacity (I think i made this word up, amphipathic properties)?

Answer 7

The 4 fused rings and the hydrocarbon tail on carbon 17 of ring D

Question 8

Fact: plant sterols arent absorbed as well

Answer 8

I need a beer

Question 9

What causes sitosterolemia?

Answer 9

defective ABCG5 or ABCG8 sterol transporter in enterocytes. This pumps excess sterols out into the lumen

Question 10

What does ezetimibe do?

Answer 10

Blocks the intestinal absorption of cholesterol at the brush border

Question 11

What cells synthesize cholesterol?

Answer 11

Nearly all except RBCs,

most is syn. in liver, intestines, adrenal cortex, reproductive tissues

Question 12

Where do the carbons come from in cholesterol?

Answer 12

acetyl coa,

Question 13

What does cholesterol Syn. use for reducing power?

Answer 13

NADPH

Question 14

Where do the cholesterol syn rxns happen?

Answer 14

cytosolic surface of smooth ER

Question 15

List the steps of cholesterol syn.?

Answer 15

2 acetyl coa___thiolase__> Acetoacetyl CoA___HMG-CoA Synthase_+acetylcoa__> HMG CoA___HMG CoA reductase__+ 2 NADPH____> Mevalonate

Question 16

What step in cholesterol syn is rate limiting?

Answer 16

HMG CoA reducase (HMG CoA to Mevalonate)
enzyme expression inhibited by cholesterol
on the cytosolic surface of smooth ER membrane
irreversible reaction bc CoA is released

Question 17

See “Mevalonate to cholesterol” the diagram on page 362 of the notes

Answer 17

this shit sucks

Question 18

How many ATP does it take to make squalence?

Answer 18

18 (3 per isoprenoid)

Question 19

What triggers the cyclization squalence resulting in lanosterol?

Answer 19

The hydroylation of squalence

Question 20

What is Smith-lemil-optiz syndrome?

Answer 20

Autosomal recessive disorder of cholesterol syn. (7dehydrocholesterol-7reductase)

Question 21

List the ways cholesterol syn is regulated?

Answer 21

sterole dependent transcriptional regulation, sterol accelerated enzyme degredation, sterol independent phosphorylation-dephosphorylation, and hormonal

Question 22

Regulation of Cholesterol gene expression (HMG CoA reductase

Answer 22

when low cholesterol levels:
SREBP2 binds to SCAP and activates the complex, and moves to golgi and SCREB is cleaved. A piece goes into the nucleus and binds to SCRE and stimulates gene expression.

Cholesterol binds and inhibits SCAP

Question 23

Regulation of cholesterol by enzyme degradation

Answer 23

in high levels of cholesterol, cholesterol binds to HMG coa reductase causing it to be degraded by ubiquintination and proteosomes

Question 24

Does phosphorylation activate or inactivate HMG CoA reductase?

Answer 24

Phosphorylation inactivates

Dephosphorylation activates

Question 25

What hormones up regulate HMG CoA reductase expression?

Answer 25

Insulin and thyroxine

Question 26

What hormones down regulate HMG CoA reductase expression?

Answer 26

glucagon and glucocorticoids

Question 27

What are statins analogues of?

Answer 27

HMG, they act as a competitive inhibitor for HMG CoA reductase

Question 28

Is the ring structure of cholesterol metabolized?

Answer 28

No, it is turned into bile salts/acids (eliminated in feces). some is modified in intestines by bacteria to become copropstanol and cholestanol

Question 29

What is in bile?

Answer 29

bile salts, phophatidyl choline

Question 30

What percentage of bile is salts in the duodenum? acids? Why?

Answer 30

50-50 bc the pKa of the hydroxyl group is around 6, the pH in the intestine is 6

Question 31

Why can bile salts act as emulsifying agents?

Answer 31

They have a polar face (hydroxyls point down) and a nonpolar face (methyls point up)

Question 32

Two most common bile acids?

Answer 32

Cholic acid and chenodeoxycholic acid

Question 33

How is cholesterol modified to make a bile salt/acid?

Answer 33

Hydroxyls are added, a double bond is reduced, the hydrocarbon tail is shortened by 3 carbons

Question 34

What is the rate limiting step of bile acid syn?

Answer 34

the addition of the hydroxyl goup to the C7 of cholesterol making 7alpha-hydroxycholesterol (via cholesterol-7-alpha-hydroxylase

Question 35

What does cholesterol-7-alpha-hydroxylase need for its reaction?

Answer 35

O2 and NADPH

Question 36

What amino acids do bile salts conjugate with? Why do they conjugate?

Answer 36

Taurine and glycine, makes them better detergents

Only the conjugated forms are found in bile (then unconjugate in intestines)

Question 37

How is a secondary bile salt produced?

Answer 37

The removal of the C7 hydroxyl

Question 38

How is bile reabsobed? How much is reabsorbed?

Answer 38

intestines: enterocyte Na+-bile salt cotransporter isoform
Blood: albumin carries it to the liver and a hepatocyte Na+-bile salt cotransporter isoform

(95%reabsorbed)

Question 39

What is enterohepatic circulation?

Answer 39

The synthesis, release and reabsoptions of bile salts

Question 40

Why do gallstones form?

Answer 40

The precipitation of cholesterol due to an imbalance in cholesterol and bile salt secretion