Flashcard Set Preview
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| 1 |
what are the 2 forms of cholesterol that exist in us and where are they found?
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1. "free" unesterified - in membrane-rich tissues like RBC and NS
2. ester form (neutral)...
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| 2 |
discuss overall structure and properties of cholesterol
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condensed 4-ring steroid ring, angular, inflexible, low water solubility --> 1 -OH group,...
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| 3 |
where in the body is cholesterol mostly made?
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liver
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| 4 |
why are vegetarian diets cholesterol free?
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*exclusively an animal product and none is produced by bacteria either
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| 5 |
what does cholesterol absorption depend on?
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bile salts and dietary intake
ex: can reach 60% in low cholesterol diet, but normally 30%
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| 6 |
what is the raw material in cholesterol synth?
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acetyl-CoA
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| 7 |
where in the cell does cholesterol synth take place?
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cytosol --> so acetyl CoA had to be shuttled via citrate to cytosol
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| 8 |
what material is needed for synthesis of HMG CoA?
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acetoacetyl CoA + acetyl-CoA
also, HMG-CoA synthase
but no ATP
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| 9 |
What is formed in the first committed step of cholesterol synthesis?
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mevalonic acid
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| 10 |
what enzyme forms mevalonic acid in first committed step?
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HMG CoA reductase:
need 2 NADPH's
CoASH gets released
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| 11 |
what are the 3 levels of regulation for mevalonic acid synthesis?
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enzyme = HMG CoA reductase
1. gene -- feedback inhibition
2. allosteric -- cholestrol is...
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| 12 |
after the 1st committed step of cholesterol synth, what happens next?
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3 phosphorylations, 1 decarboxylation -- get isopentenyl-pyrophosphate and then dimethylallyl...
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| 13 |
how is squalene formed? what is special about it?
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it's formed from 6 5-C dimethylallyl pyrophosphates...special because first intermediate...
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| 14 |
what happens once squalene is formed?
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gets cyclized to lanosterol - which is the 1st steroid product
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| 15 |
what enzyme cyclizes squalene and what is needed?
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squalene mono-oxygenase is a cyt P-450, so it forms an -OH group...need O2 and NADPH
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| 16 |
what effect does high insulin levels have on cholesterol synthesis?
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high insulin = active cholesterol synthesis
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| 17 |
free cholesterol inhibits cholesterol synthesis at what 2 levels?
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transcriptional (gene) level and
post-transcriptional (covalent modification) level
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| 18 |
what residue on HMG CoA reductase gets phosphorylated and dephosphorylated to change activity...
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serine!!!
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| 19 |
what is the effect of increased levels of glucagon on HMG CoA reductase?
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decreases production of enzyme
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| 20 |
what are some drug examples that can be used to reduce cholesterol production and what is their...
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lova-, simva-, and mevastatin - they are reversible competitive inhibitors of HMG CoA reductase...
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| 21 |
what are the 4 principal isoprenoids made by humans?
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ubiquinone, dolichol, side chain of Heme a, and farnesyl/geranyl groups
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| 22 |
what is the function of ubiquinone?
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electron transport in mitochondrial membrane
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| 23 |
what is the function of dolichol?
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synthesis of N-linked oligosaccharides of glycoproteins
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| 24 |
what is the fn of side chain of heme a?
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prosthetic group of cytochrome a/a3
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| 25 |
what is the fn of farnesyl/geranyl groups?
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they are membrane-protein anchors bc of their long tails
farnesyl - 15 C's
geranyl - 10 C's
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| 26 |
what enzyme is involved in anchoring proteins into membrane via farnesyl group? why is...
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farnesyl transferase -- moves 15-C unit to protein
attractive target for inhibition in cancer...
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| 27 |
plants produce a far greater range of isoprenoids than we do...give 2 examples
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1. all our fat-soluble vitamins (ADEK) are isoprenoids
2. phytanic acid -- branched chain...
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| 28 |
what is the most abundant form of vit D?
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vitamin D3 or cholecalciferol - it's a prohormone
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| 29 |
what intermediate of cholesterol biosynthesis gives rise to cholecalciferol?
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7-dehydrocholesterol
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| 30 |
what are the fns of cholecalciferol?
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regulation of Ca and P metabolism, esp in matrix of bone
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| 31 |
The steroid nucleus of cholesterol can't be degraded by humans...so what happens to it?
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dispose of cholesterol via biliary system, either by itself or after conversion to soluble...
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| 32 |
bile acid synthesis has control at the first step via what 2 genes?
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7-a-hydroxylase gene
upstream via HMG-CoA reductase gene
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| 33 |
what are the regulators of 7-a-hydroxylase?
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cholic acid (product) is a negative regulator
cholesterol (substrate) is a positive...
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| 34 |
what are the 2 primary bile salts from the liver and which is more abundant?
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cholic acid and chenodeoxycholic acid
cholic acid more abundant
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| 35 |
primary bile salts are released from the liver after conjugation with one of what 2 molecules? ...
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glycine and taurine
glycine: taurine ... 3:1
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| 36 |
which bile salt is more acidic and what makes this so?
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taurochenodeoxycholic acid is the more powerful acid that dissociates easily due to SO4 group...
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| 37 |
what enzyme catalyzes the committed step of bile acid synthesis?
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7-a-hydroxylase
introduces an -OH at position 7 of cholesterol
membrane-bound so microsomal
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| 38 |
7-a-hydroxylase is a mixed function mono-oxygenase type enzyme...what does that mean?
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requires molecular O2, NADPH, cyto P-450, and ascorbic acid!
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| 39 |
why do hypothyroid pts have elevated plasma cholesterol levels?
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b/c lack of thyroid hormones leads to decreased activity of 7-a-hydroxylase, reduced conversion...
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