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Biochem > Cholesterol Biosynthesis, Transport and Genetics > Flashcards

Cholesterol Biosynthesis, Transport and Genetics Flashcards

1
Q

What is cholesterol required as a precursor for

A

-vitamin D
-steroids
-bile salts

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2
Q

what molecule is a major structural component in myelin sheaths

A

cholesterol

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3
Q

what synthesizes myelin sheaths (In PNS and CNS)

A

glial cells
PNS- Schwann cells
CNS- oligodenrocytes

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4
Q

what molecule produces cholesterol

A

acetyl CoA

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5
Q

describe the chemical structure of steroids

A

4 hydrocarbon rings

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6
Q

describe the cholesterol chemical structure

A

4 hydrocarbon rings with a hydrocarbon tail and a hydrophilic region

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7
Q

where is cholesterol synthesized

A

mainly the liver and small intestine, also in adrenal glands and gonads

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8
Q

how much cholesterol does an average adult synthesize daily

A

800 mg

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9
Q

what are the levels for desirable and high total cholesterol

A

-desirable: under 200
- high: over 240

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10
Q

what are the good and high levels of LDL cholesterol

A

good: 100-120
high: 160-190

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11
Q

what are the good and undesirable levels of HDL cholesterol

A

good: over 60
undesirable: under 40

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12
Q

what are the 3 stages in de novo biosynthesis of cholesterol

A
  1. synthesis of isopentenyl phosphate
  2. condensation of 6 molecules of isopentyl pyrophosphate to form squalene
  3. cyclization of squalene to form the steroid 4-ring structure, which rearranges to form ianosterol which is then converted into cholesterol
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13
Q

explain the first step of de novo biosynthesis of cholesterol in detail

A

acetoacetyl CoA combines with acetyl CoA to form HMG CoA. HMG CoA is converted to mevalonate in the cytosol by HMG CoA reductase. mevalonate is then converted into isopentyl pyrophosphate

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14
Q

what is the rate limiting step in the regulation of cholesterol biosynthesis

A

the production of mevalonate from HMG-CoA by HMG CoA reductase

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15
Q

what is HMG CoA reductase

A

enzyme that catalyzes the first step of cholesterol biosynthesis. it is tightly regulated at the transcriptional and translational levels

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16
Q

what is the rate of synthesis of reductase mRNA controlled by

A

a transcription factor called sterol regulatory element bind protein (SREBP)

17
Q

how does SREBP work

A

it is regulated by levels of cholesterol available by the INSIG and SCAP proteins that bind cholesterol

18
Q

what is the rate of translation of reductase mRNA inhibited by

A

metabolites derived from mevalonate and dietary cholesterol

19
Q

what is the degradation of reductase tightly controlled by

A

lanosterol

20
Q

where is the SREBP, SCAP, and insig protein complex located when they stay together

A

ER membrane

21
Q

where is the SREBP and SCAP complex located when it dissociates from INSIG

A

golgi

22
Q

what do lanosterol and acetyl CoA carboxylase have in common

A

they catalyze a similar step in their respective pathways (cholesterol biosynthesis and fatty acid biosynthesis) and are switched off by a AMP activated protein kinase. their processes cease when ATP is low

23
Q

what are the drugs that regulate cholesterol synthesis

A

stains and bisphosphonates

24
Q

how do statins work

A

competitively inhibiting HMG CoA reductase thus reducing the amount of mevalonate produced

25
Q

when does cholesterol synthesis occur

A

at night

26
Q

what is the extra benefit of statins

A

inhibit bone resorption by osteoclasts because they also inhibit prenylated proteins

27
Q

what is necessary in the diet to absorb dietary cholesterol

A

fat

28
Q

what are bisphosphonates used for

A

treating bone disorders to inhibit osteoclast resorption of bone

29
Q

what is a side effect os bisphosphonates

A

osteonecrosis of jaw

30
Q

what part of the de novo pathway for cholesterol biosynthesis do bisphosphonates work

A

the isopentenyl-5-prophosphate

31
Q

what happens in protein prenylation

A

post translational modification of proteins that adds a hydrophobic molecule to target proteins that anchors the protein to the membrane surface

32
Q

describe the role of prenylation is osteoclast function

A

small GTPase localize to specific membrane compartments and assist in cytoskeleton rearrangement needed to form the sealing zone

33
Q

where are bile and bile salts made and stored

A

they are made in the liver and stored in the gallbladder

34
Q

when does the gallbladder release bile

A

after we eat and fat is present in the digestive tract

35
Q

what are functions of bile and bile salts

A
  • aid digestion by breaking down fats
    -help absorb fat-soluble vitamins
    -eliminate waste products
36
Q

what is bile composed of

A

water, lecithin, bile salts and cholesterol

37
Q

what is the major way that cholesterol is eliminated from the body

A

bile salts

38
Q

how does the amphipathic nature of bile salts contribute to their function

A

emulsification of lipid aggregates and solubilization and transport of lipids in an aqueous environment

Biochem (34 decks)

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