cholesterol synthesis

what is the main organ of cholesterol synthesis

• liver

what is the precursor of many steroid hormones?

• cholesterol

what are the main sources of acetyl CoA for biosynthesis of cholesterol

• Stage 1 TCA cycle

  • pyruvate → acetyl CoA

• beta-oxidation of fats

• amino acids

the enzymes used in the biosynthesis of cholesterol are found where?

• cytosol

• endoplasmic reticulum

why does cholesterol synthesis occur?

• low levels of cholesterol in cell

list the steps to make cholesterol

1. acetyl CoA + acetyl CoA → acetoacetyl CoA

2. acetoacetyl CoA + acetyl CoA → HMG CoA

3. HMG CoA → mevalonic acid

4. mevalonic acid → isopentyl pyrophosphate (C5)

5. isopentyl pyrophosphate (C5) → squalene (C30)

6. squalene (C30) → lanosterol (C30)

7. lanosterol (C30) → cholesterol (C27)

what is the rate limiting step in cholesterol synthesis? what enzyme is used? what type of reaction is it?

• HMG CoA → mevalonic acid

• HMG CoA reductase

• redox reaction

  • 2NADPH + 2H+ → 2NADP+

what is a common side effect of statins and why?

• dry ear

  • decrease HMG CoA reductase → decrease squalene = wax

what type of lipid is squalene

• C30

• open chain

• wax

describe lanosterol

• C30

• sterol ring formed

beta-ketothiolase catalyzes what reaction

a) acetyl CoA + acetyl CoA → acetoacetyl CoA

b) HMG CoA → mevalonic acid

c) acetoacetyl CoA + acetyl CoA → HMG CoA

d) mevalonic acid → isopentyl pyrophosphate (C5)

a) acetyl CoA + acetyl CoA → acetoacetyl CoA

HMG-CoA synthase is used for what reaction

a) acetyl CoA + acetyl CoA → acetoacetyl CoA

b) HMG CoA → mevalonic acid

c) acetoacetyl CoA + acetyl CoA → HMG CoA

d) mevalonic acid → isopentyl pyrophosphate (C5)

c) acetoacetyl CoA + acetyl CoA → HMG CoA

SATA: HMG CoA synthase catalyzes

a) glucose synthesis

b) ketone body synthesis

c) cholesterol synthesis

d) amino acid synthesis

b) ketone body synthesis

c) cholesterol synthesis

Acyl CoA cholesterol acyltransferase (ACAT)

• catalyzes synthesis of cholesterol esters from cholesterol

how can cholesterol be “protected” ?

• protect as cholesterol ester

  • ester prevents oxidation of original secondary alcohol

• can be hydrolyzes to obtain cholesterol

why are statins prescribed?

• lower cholesterol

what are statins ? How does its structure help its function?

• competitive inhibitors of HMG CoA reductase

  • suppress synthesis of cholesterol → only dietary cholesterol

• lactone ring opens (pro drug) → active drug → portion is similar to mevalonate → alters Km & binds more strongly to active site than native substrate

reduction of dihydroxyacetone phosphate yields ..

• glycerol 3-phosphate (alcohol)

glycerol 3-phosphate dehydrogenase

• dihydroxyacetone phosphate → glycerol 3-phosphate

  • NADH → NAD+

  • redox

Feedback regulation of cholesterol synthesis is mainly controlled at the step catalyzed by the enzyme:

1. HMG-mutase.

2. HMG transferase.

3. farnesyl reductase.

4. 3-hydroxy-3-methylglutaryl (HMG) CoA reductase.

5. geranyl transferase

4. 3-hydroxy-3-methylglutaryl (HMG) CoA reductase.

Which compound is NOT an intermediate in the synthesis of lanosterol from acetyl-CoA?

1. malonyl-CoA

2. isopentenyl pyrophosphate

3. squalene

4. mevalonate

1. malonyl-CoA

HMG CoA is synthesized from acetyl CoA and:

1. oxaloacetate.

2. acetoacetyl CoA.

3. farnesyl pyrophosphate.

4. mevalonate.

5. acetyl CoA.

2. acetoacetyl CoA.

Which compound(s) is derived from a sterol?

1. gangliosides

2. geraniol

3. bile salts

4. phosphatidylglycerol

5. prostaglandins

4. bile salts

The major carrier(s) of dietary fat from the intestine is/are:

1. VLDL.

2. LDL.

3. HDL.

4. IDL.

5. chylomicrons.

5. chylomicrons.

Cholesterol is synthesized from:

1. lipoic acid.

2. oxalate.

3. malate.

4. choline.

5. acetyl-CoA.

5. acetyl-CoA.

Which contains the highest percentage of cholesteryl esters?

1. chylomicrons

2. HDL

3. VLDL

4. LDL

4. LDL

The committed step in cholesterol formation is the synthesis of:

1. isoprene.

2. squalene.

3. HMG CoA.

4. mevalonate.

5. 3-isopentenyl pyrophosphate.

4. mevalonate.

How does the number of carbon atoms change upon synthesis of cholesterol starting from mevalonate?

1. C₅ → C₆ → C₁₀ → C₁₅ → C₃₀

2. C₅ → C₁₀ → C₁₅ → C₃₀

3. C₆ → C₅ → C₁₀ → C₁₅ → C₃₀

4. C₆ → C₅ → C₁₀ → C₁₅ → C₃₀ → C₂₇

5. C₅ → C₁₀ → C₁₅ → C₃₀ → C₂₇

4. C₆ → C₅ → C₁₀ → C₁₅ → C₃₀ → C₂₇

A 30-carbon precursor of the steroid nucleus is:

1. farnesyl pyrophosphate.

2. isopentenyl pyrophosphate.

3. geranyl pyrophosphate.

4. squalene.

5. lysolecithin.

4. squalene.