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29 Cards in this Set
- Front
- Back
What are the synthesis steps, with associated enzymes, leading to cholesterol synthesis?
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HMG-CoA (by HMG-CoA Synthase)
Mevalonic Acid (by HMG-CoA Reductase *rate limiting) Cholesterol (from Mevalonic acid) |
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What is the rate limiting enzyme in cholesterol synthesis?
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HMG-CoA Reductase
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How is cholesterol eliminated?
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As bile salts
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What are the functions of cholesterol?
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structural component of cell membranes, precursor to bile acids, steroid hormones, and vitamin D
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Which organ is most responsible for regulating cholesterol homeostasis?
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The liver
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What are the body's major sources of cholesterol?
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dietary cholesterol, de novo cholesterol by extrahepatic tissues (HDL) and the liver
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How is cholesterol eliminated from the liver?
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as unmodified cholesterol in bile, converted to bile salts and secreted into the intestinal lumen, becomes a component of plasma lipoproteins (e.g., VLDLs)
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What is a cholesterol ester (CE)?
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an esterified cholesterol, which makes it more hydrophobic than free cholesterol
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How are cholesterol and CEs transported?
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in lipoprotein particles or bile micelles
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Where is cholesterol synthesized?
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by virtually all tissues, but liver, intestine, adrenal cortex, and reproductive tissues make most (this occurs in the cytoplasm)
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Under what conditions is cholesterol synthesized?
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during the fed state, where ATP and NADPH are available
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How is HMG CoA synthesized?
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Acetyl CoA → acetoacetyl CoA (HMG CoA synthase) → HMG CoA
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How is mevalonic acid synthesized from HMG CoA?
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HMG CoA (HMG CoA reductase + 2 NADPH) → mevalonic acid
-irreversible- |
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How is cholesterol synthesized?
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19 enzyme pathway that is very ATP, NADPH dependent
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How is cholesterol synthesis regulated (rate limiting enzyme)?
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HMG-CoA reductase (active in fed state, when dephosphorylated)
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What is the effect of SREBP on HMG-CoA reductase?
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a transcription factor that binds the HMG-CoA reductase gene, increases expression → more cholesterol
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What effect does cholesterol have on the mRNA of HMG-CoA reductase?
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shortens its protein half life → less cholesterol
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What effect does insulin and glucagon have on HMG-CoA reductase?
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insulin activates HMG-CoA reductase by dephosphorylation → more cholesterol, glucagon has an opposite effect
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What effect does obesity have on cholesterol synthesis?
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obesity leads to insulin resistance in muscle and adipose, but NOT liver → accelerated hepatic de novo cholesterol synthesis
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What do statin drugs do to plasma cholesterol levels? How do they do this?
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statins (HMG-CoA analogs) lower plasma cholesterol by competetively inhibiting HMG-CoA reductase
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What is the rate limiting enzyme of bile acid synthesis and what does it do?
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cholesterol 7-(alpha)-hydroxylase, adds hydroxyl group at 7 position of steroid ring
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7-(alpha)-hydroxyl cholesterol is converted to what two primary bile acids?
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chenodeoxycholic acid, cholic acid
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Bile acids are conjugated with two amino acids to form two bile salts. What are they?
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chenodeoxycholic acid + taurine → taurochenodeoxycholic acid
cholic acid + glycine → glycholic acid |
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What are bile salts taurochenodeoxycholic and glycholic acid used for?
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digestion (emulsification) and absorption (micelles) of dietary lipids, and the excretion of hydrophobic waste in bile
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What do intestinal flora do to bile salts?
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deconjugate them back to bile acids, convert primary bile acids to secondary bile acids, deoxycholic and lithocholic acids
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Which are better emulsifiers: bile acids or bile salts?
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bile salts (more polar)
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Where do primary and secondary bile acids and bile salts get reabsorbed?
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the ileum
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What are the treatments for hypercholesterolemia?
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statin drungs, weight loss, cholestyramine
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What is cholestyramine's effect on cholesterol?
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prevents reabsoption of bile salts, thereby forcing the liver to use more cholesterol for bile salt synthesis (lowers cholesterol)
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