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Biochem > Cholesterol Metabolism > Flashcards

Cholesterol Metabolism Flashcards

1
Q

What are some the functions of cholesterol?

A
  • Essential components of cell membranes
  • Precursor for bile salts
  • Precursor for steroid hormones
  • Regulates the activity of proteins
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2
Q

What part of cholesterol gives it its amphipathic qualities?

A

The hydroxyl (OH) group

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3
Q

What are the different sources of cholesterol?

A
  • Endogenous sources (major source)
  • Dietary sources
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4
Q

What are some examples of endogenous sources of cholesterol?

A

The liver synthesizes 1 gram of cholesterol daily

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5
Q

What are some examples of dietary sources of cholesterol?

A
  • Egg
  • Cheeseburger
  • etc…
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6
Q

How do clinical drugs reduce cholesterol levels?

A

They target both endogenous and dietary sources of cholesterol

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7
Q

Giver a BRIEF overview of cholesterol biosynthesis

A
  • Occurs predominantly in the liver
  • Increased by insulin and reduced by glucagon
  • Biosynthetic enzymes = in the cytosol
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8
Q

Why are cholesterol biosynthetic enzymes found in the cytosol?

A

Allows you to segregate biosynthetic products (which require energy) from energy producing products

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9
Q

What is the first stage in cholesterol biosynthesis?

A

Acetyl-CoA —> HMG-CoA —> Mevalonate
- Acetyl-CoA must make its way from the matrix to the cytoplasm (how does it do this?)
- In the cytoplasm acetyl-CoA is converted to isoprene units
- HMG-CoA is made from 3 molecules of acetyl-CoA by HMG-CoA synthase
- HMG-CoA reductase takes HMG-CoA and turns it into mevalonate

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10
Q

What is the second stage in cholesterol biosynthesis?

A

Mevalonate —> Two activated isoprene units
- 4 step reaction

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11
Q

Describe the 4 step reaction that turns mevalonate into two isoprene units

A
  1. Mevalonate phosphotransferase adds the first phosphate (result: phosphomevalonate)
  2. Phosphomevalonate kinase adds the second phosphate (result: 5-pyrophosphomevalonate)
  3. Pyrophosphomevalonate decarboxylase decarboxylates and dehydrates to produce the isoprene unit (result: isopentenyl pyrophosphate)
    ATP = cofactor
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12
Q

What is the third stage in cholesterol biosynthesis?

A

Condensation of 6 activated isoprenes make squalene (30C)

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13
Q

What is the fourth stage in cholesterol biosynthesis?

A

Cyclization of squalene to make lanosterol and conversion of lanosterol into cholesterol

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14
Q

How is cholesterol biosynthesis regulated?

A
  1. Rapid regulation
  2. Long-term regulation
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15
Q

Describe rapid regulation of cholesterol biosynthesis

A

Phosphorylation by AMP activated protein kinase (AMPK) inactivates HMG-CoA reductase
HMG-CoA reductase turns HMG-CoA into mevalonate

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16
Q

Describe long-term regulation of cholesterol biosynthesis

A

Regulation of HG-CoA reductase transcription

17
Q

Describe the regulation of HMG-CoA reductase transcription

A
18
Q

How is cholesterol transported to target tissues

A
  • Dietary cholesterol is packaged into chylomicrons
  • Lipoprotein lipase cleaves triglycerides in chylomicrons
  • Cholesterol-rich chylomicron remnants are taken up by the liver
  • In the liver cholesterol and cholesterol esters are incorporated into VLDL that are released into the bloodstream
  • In the bloodstream lipoprotein lipase cleaves triglycerides in VLDL to generate LDL
  • LDL is taken up by peripheral tissues by endocytosis
19
Q

How is LDL recognized and taken up by peripheral tissues

A
  • LDL receptors on tissue recognize and bind apolipoprotien B100 on LDL
20
Q

Describe the structure of a VLDL

A
  • Cholesterol = confined to the phospholipid monolayer
  • Cholesterol esters = packed into the hydrophobic lipoprotein interior
21
Q

What is the difference between good cholesterol and bad cholesterol?

A
  • Bad cholesterol = LDL
  • Good cholesterol = HDL
    You want high levels of HDL and low levels of LDL
22
Q

Why is LDL bad?

A

High levels of LDL circulating in the blood stream leads to atherosclerosis and coronary heart disease

23
Q

What is atherosclerosis?

A

The hardening and thickening of arteries and restricted blood flow caused by deposition of lipids (cholesterol) within arteries

24
Q

How can you reduce blood cholesterol levels?

A
  1. Diet
  2. Drugs
25
Q

What are statins?

A

HMG-CoA reductase inhibitors
What does HMG-CoA reductase do?

26
Q

What is another inhibitor that can Lower LDL levels?

A
  • PCSK9 inhibitors
  • PCSK9 is secreted by the liver and binds to LDL receptor and enhances its degradation by lysosomes within cells
  • PCSK9 inhibitors block this function and reduce LDL receptor degradation allowing it to be recycled to the plasma membrane to take up additional LDL

Biochem (27 decks)

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