Metabolism 8: Cholesterol and Bile Acids

Question 1

What is cholesterol used for?

Answer 1

Component of cell membranes
Stored as cholesterol Ester
Precursor for bile acids in liver
Precursor for steroid hormones of endocrine tissues

Question 2

What are steroid hormones that use cholesterol?

Answer 2

progesterone
estradiol
Testosterone
Cortisol
Aldosteron
Vitamin D3
Dehydroepiandrosterone

Question 3

What happens to cholesterol/cholesterol esters taken in from the diet?

Answer 3

Taken along with dietary TAG in the intestines and pakcaged into chylomicrons

Question 4

What happens to cholesterol that is synthesized int he body?

Answer 4

Packaged in the liver along with TAGs into VLDL (Very low density lipoproteins)

Becomes IDL, LDL as it is transported to peripheral tissues

Question 5

What is mevalonate?

Answer 5

intermediate in cholesterol biosynthesis formed in the rxn caalyzed by HMG-CoA Reductase

Question 6

What is HMG-CoA REductase?

Answer 6

It is the rate limiting enzyme in cholesterol biosynthesis that converts HMG-CoA to mevalonate using 2 NADPH

Question 7

What does the 6C compound Mevalonate convert to eventually?

Answer 7

Lanosterol (30C)

Question 8

How is mevalonate converted to Lanosterol?

Answer 8

Mevalonate (6C) -> Isopentenylpyrophosphate (5C) -> Dimethylallylpyrophosphate (5C) -> Farnesypyrophosphate(15C)
2 molecules of farnesyl pyrophosphate ->form Squalene (30C) -> Squalene is converted to Lanosterol (30C) via cyclization

Question 9

What does lanosterol(30C) eventually convert into?

Answer 9

Cholesterol (27C)

Question 10

WhatWhat inhibits HMG-CoA REductase?

Answer 10

AMP, glucagon, cholesterol, mevalonate(neg feedback), CoASH

Question 11

What activates HMG-CoA REductase?

Answer 11

Insulin

Question 12

What inhibits mRNA production of HMG-CoA REductase?

Answer 12

Sterols (cholesterol)

Question 13

What inhibits the translation of the mRNA for HMG-CoA Reductase?

Answer 13

Nonsterol Metabolite from mevalonate

Question 14

What increases enzyme degradation of HMG-CoA Reductase?

Answer 14

Mevalonate, cholesterol

Question 15

What increased phosphorylation and thus inhibition of HMG-CoA Reductase?

Answer 15

AMP, glucagon

Question 16

Where and how are bile salts made?

Answer 16

Made in the liver using cholesterol

Question 17

What is the rate limiting enzyme in bile acid biosynthesis?

Answer 17

7-a-hydroxylase (Cholesterol -> Bile acids)

Question 18

What enzymes convert cholesterol into their storage ester forms?

Answer 18

ACAT (Cholesterol -> cholesterol esters)

Question 19

What does excess cholesterol lead to?

Answer 19

Increased cholesterol use and inhibits cholesterol synthesis

Inhibits HMG-CoA Reductase- dec synthesis
Activates ACAT- inc storage/use
Activates 7-a-hydroxylase- inc bile acid synthesis

Question 20

What does cholesterol deprivation lead to?

Answer 20

Activates cholesterol synthesis and inhibits cholesterol use

Activates HMG-CoA Reductase- inc synthesis
Inhibit ACAT: dec storage/use
Inhibit 7-a-hydroxylase dec bile acid synthesis/use

Question 21

What are the 3 rate limiting enzymes in lipid metabolism?

Answer 21

ACAT: cholesterol storage
HSTL: hydrolyze TAG to FA and glycerol
CPT-1: transfer fatty acyl-CoA into mitochondria

Question 22

What is the rate limiting enzyme for fatty acid biosynthesis?

Answer 22

Acetyl-CoA Carboxylase