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What is the rate-limiting enzyme for cholesterol biosynthesis?
HMG CoA-reducatase
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What is the location of cholesterol biosynthesis?
Liver--in the cytoplasm
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What does HMG CoA reductase do?
Converts HMG CoA into mevalonate
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HMG CoA is active in the phos or dephos form?
Dephos
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What type of drugs inhibit HMG CoA reductase?
Statins
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What are the consequences of inhibiting HMG CoA reductase?
Lowers intracellular cholesterol and upregulates apo B/E receptors which are used for the import of cholesterol into cells
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What converts cholesterol into cholesterol esters?
ACAT
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What 3 things are derived from cholesterol?
Vitamin D, Steroid hormones, and bile salts
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How much cholesterol is synthesized by humans daily?
1 g/day
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How much circulating cholesterol is in its alcohol form? What form is it found in the majority of the time?
30% in alcohol form. The majority is stored as cholesterol esters, coupled with long chain fatty acids.
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How are cholesterol esters transported?
Lipoproteins, ie chylomicron
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The biosynthesis of 1 mol of cholesterol requires how many moles of acetyl CoA? ATP? NADPH?
- 18 mol acetyl CoA
- 36 mol ATP
- 16 mol NADPH
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How is HMG-CoA reductase synthetase stimulated? Inhibited?
Stimulated by well fed state, inhibited by dietary cholesterol intake
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What 15 carbon molecule is mevalonate (6C) converted into?
farnesyl pyrophosphate
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In farnesyl pyrophosphate synthesis, what 'shunt' allows you to convert 3,3-dimethylallyl pyrophosphate to HMG CoA?
Trans-methylglutaconate shunt
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When 2 farnesyl pyrophosphate molecules come together, what molecule is made?
Squalene (30C)
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What is the pathway involving oxysterols activating LXR?
LXR (Liver X receptor) can activate SREBP. In the absence of sterols, SCAP takes SREBP to its protease to activate it. This turns on gene transcription and cholesterol biosynthesis. When sterol levels are high, SCAP is inhibited and no genes are transcribed for cholesterol biosynthesis.
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What hormones activate cholesterol syntheis? Inactivate?
Insulin and T3 activate, glucagon and cortisol inactivate
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