Cholesterol Biosynthesis Flashcards

1
Q

Cholesterol has a crucial role in the structure of ____

A

Membranes

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2
Q

What is cholesterol a precursor for?

A

Steroid hormones and bile salts

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3
Q

Why is cholesterol not required in the diet?

A

Because all cells can synthesize cholesterol from simple precursors

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4
Q

What is Smith-Lemli Opitz Syndrome?

A

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

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5
Q

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

A

The liver

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6
Q

What is the fate of cholesterol produced by the liver?

A

Small amount incorporated into hepatocyte membranes, most exported

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7
Q

What compound is cholesterol made of?

A

Acetyl coA (4)

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8
Q

What is the rate limiting step of cholesterol synthesis?

A

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

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9
Q

What enzymes do statins inhibit?

A

HMG-CoA Reductase

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10
Q

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

A
  • Cholesterol inhibits the enzyme allosterically via feedback inhibition
  • Cholesterol and cholesterol derivatives promote rapid degradation of the enzyme via ubiquitin/proteasome
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11
Q

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

A
  • Cholesterol can inhibits its own transcription in the nucleus
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12
Q

Describe the hormonal regulation of HMG-CoA reductsae.

A
  • 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
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13
Q

What enzyme is responsible for esterifying cholesterol?

A

Acyl-CoA-Cholesterol Acyl Transferase (ACAT)

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14
Q

What happens to newly formed cholesterol in the liver?

A

It is esterified and packed into VLDL

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15
Q

What is the purpose of esterifying cholesterol?

A

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

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16
Q

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

A

Liver

Gallbladder

17
Q

What do bile salts do?

A

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.

18
Q

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

A

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

19
Q

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

A

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.

20
Q

Describe the recycling of bile salts.

A
  • 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
21
Q

Is vitamin D a hormone?

A

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

22
Q

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

A

Rickets

Osteomalacia

23
Q

Vitamin D is formed in the ______ from ______

A

Skin

Cholesterol

24
Q

What are the effects of Vitamin D on the:

  • Intestine
  • Bone
  • Kidney
A
  • Absorb calcium
  • Promote calcification of bone
  • Increase resorption of Ca2+ from kidney
25
Q

What are the 4 basic steps of cholesterol synthesis?

A
26
Q

Which step of cholesterol synthesis is the committed step?

A

Formation of acetoacetyl coA by thiolase

27
Q

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.

A

Different isozyme