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23 Cards in this Set
- Front
- Back
overall equation for cholesterol synth
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18 ACoA, 18 NADPH, 18 ATP, 4 O2
cholesterol, 18 NADP, 18 ADP, 18 Pi, 9 CO2 |
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solubility of cholesterol
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most insol substance
.2 mg/dL yet plasma conc is similar to blood glucose |
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structure of cholesterol
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27 C's
4 rings hydroxy at 3 |
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circulation of cholesterol
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synthed in liver
circulate in lipoproteins -as chol esters -usually with linoleic acid |
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cholesterol in membranes
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100% in free (hydroxy) form
assoc w/sphingomyeline |
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cholesterol in bile
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disposal
mostly free cholesterol |
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excretion of cholesterol
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bile only
no enzyme to break rings can't excrete in urine or breath |
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functions of cholesterol
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membrane fluidity
-assoc w/sphingomyeline -form rafts -OH sticks out into interstit bile salts steroids |
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location of cholesterol production
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all cells (except RBC)
cytoplasm (mostly ER) especially liver adrenal, testes, ovaries also (pools of chol stored here) |
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intermediates in cholesterol synth
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isoprenoid's
ubiquinone (mito ETC) Dolichol (synth oligosacchs for GPs) Farnesyl & geranyl (anchor fctn in memb proteins) poss side effects for statins |
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cholesterol in brain
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not cross BBB
mostly in glials synthed in brain for brain use convert to 24 hydroxy & sent to liver |
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24 hydroxylase
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catabolic enzyme for cholesterol in liver
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general rxn for Cholesterol synth
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ACoA
HMG CoA (HMG CoA reductase is rate limit) mevalonic acid PPMV isoprenonyl (geranyl) (farnesyl) ... cholesterol 25-30 rxns |
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first step cholesterol synth
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move ACoA into cyto
via citrate |
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production of HMG CoA
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ACoA (after move into cyto)
thiolase & ACoA synthetase gives acetoacytal CoA(intermed) HMG CoA synthase (aka condensing enzyme- in mito will make ketone) generates HMG CoA |
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fate of HMG CoA in cholesterol synthesis
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gets reduced to mevalonic acid
HMG CoA reductase rate limiting step uses 2 NADPH |
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fate of mevalonic acid
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kinase generates PPMV
uses LOTS of ATP very high energy molecule |
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generation of isoprene molecules in cholesterol synth
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decarboxylate PPMV
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generation of geranyl in cholesterol
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isomerise & condense Isoprene
uses 2 isoprenes |
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characteristics of geranyl
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10C fatty acyl
high energy put on proteins increases hydrophobicity |
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characteristics of farnesyl
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from geranyl
(from isoprenes) changes protein characteristics |
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bisphosphanates
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tx osteoporosis & Ca
block production of farnesyl & geranyl inactivates GTPase decreases bone resorp SE: mandibular resorption (doesn't act in liver so no effect on chol) |
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regulation of cholesterol synthesis
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increased cholesterol:
-Plate HMG CoA reduct -inhib catalytic site -enhance proteolysis of HMGCoA -block translation HMG reductase -repress HMGCoA expression via SREBP low chol: -activate SREB -turns on transcription of reductase |