Cholesterol Biosynthesis

Question 1

Cholesterol has a crucial role in the structure of ____

Answer 1

Membranes

Question 2

What is cholesterol a precursor for?

Answer 2

Steroid hormones and bile salts

Question 3

Why is cholesterol not required in the diet?

Answer 3

Because all cells can synthesize cholesterol from simple precursors

Question 4

What is Smith-Lemli Opitz Syndrome?

Answer 4

Syndrome with multiple malformations and mental disability associated with defective cholesterol biosynthesis due to defective enzyme in final step of cholesterol synthesis pathway

Question 5

Although all cells can synthesize cholesterol, where is it primarily made?

Answer 5

The liver

Question 6

What is the fate of cholesterol produced by the liver?

Answer 6

Small amount incorporated into hepatocyte membranes, most exported

Question 7

What compound is cholesterol made of?

Answer 7

Acetyl coA (4)

Question 8

What is the rate limiting step of cholesterol synthesis?

Answer 8

reduction of HMG-CoA to mevalonate by HMG-CoA reductase

Question 9

What enzymes do statins inhibit?

Answer 9

HMG-CoA Reductase

Question 10

How is HMG-CoA reductase regualted at the level of the enzyme?

Answer 10

• Cholesterol inhibits the enzyme allosterically via feedback inhibition
• Cholesterol and cholesterol derivatives promote rapid degradation of the enzyme via ubiquitin/proteasome

Question 11

How is HMG-CoA reductase regulated at the level of the genome?

Answer 11

• Cholesterol can inhibits its own transcription in the nucleus

Question 12

Describe the hormonal regulation of HMG-CoA reductsae.

Answer 12

• The enzyme is inhibited when it is phosphorylated.
• Glucagon –> stimultes kinase –> phosphorylates HMG-CoA reductase –> inhibited
• Insulin –> stimulates phosphatase –> removes phosphate –> HMG-CoA reductsae active

Question 13

What enzyme is responsible for esterifying cholesterol?

Answer 13

Acyl-CoA-Cholesterol Acyl Transferase (ACAT)

Question 14

What happens to newly formed cholesterol in the liver?

Answer 14

It is esterified and packed into VLDL

Question 15

What is the purpose of esterifying cholesterol?

Answer 15

Makes it less polar so it is able to enter lipid droplet

Question 16

Bile salts are made in the ____ and secreted into the ____

Answer 16

Liver

Gallbladder

Question 17

What do bile salts do?

Answer 17

They are detergents - they are able to solubilize lipids b/c they have both non-polar and polar groups (amphipathic). All the polar groups are in the same plane, creating separation of polar and non-polar areas. This causes them to form micelles in solution.

Question 18

Primary bile salts are made by the body. What are secondary bile salts?

Answer 18

Gut bacteria can act on primary bile salts to make secondary bile salts

Question 19

What is the difference between a bile acid and bile salt?

Answer 19

Although many use them interchangeabley, a bile acid is what is made by the body and a bile salt is a bile acid conjugated with amino acids.

Question 20

Describe the recycling of bile salts.

Answer 20

• Synthesized liver –> stored gallbaldder –> released to intestines when needed –> active transport of bile salts from ileum back to liver
• Some bile salt spillsover to systemic circulation and is excreted in the kidney, so there is some need to synthesize new bile salts daily but not much as most is recycled

Question 21

Is vitamin D a hormone?

Answer 21

Yes - it is produced at one site, transported through blood and exerts its effects at distant site –> HORMONE

Question 22

Vitamin D deficiency is called ____ in children and ____ in adults

Answer 22

Rickets

Osteomalacia

Question 23

Vitamin D is formed in the ______ from ______

Answer 23

Skin

Cholesterol

Question 24

What are the effects of Vitamin D on the:

• Intestine
• Bone
• Kidney

Answer 24

• Absorb calcium
• Promote calcification of bone
• Increase resorption of Ca2+ from kidney

Question 25

What are the 4 basic steps of cholesterol synthesis?

Answer 25

Question 26

Which step of cholesterol synthesis is the committed step?

Answer 26

Formation of acetoacetyl coA by thiolase

Question 27

The cytosolic HMG-CoA synthase in the cholesterol biosynthesis pathway is (the same/different) from the HMG-coA synthase in the mitochondria used for ketone body formation.

Answer 27

Different isozyme