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23 Cards in this Set

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overall equation for cholesterol synth
18 ACoA, 18 NADPH, 18 ATP, 4 O2

cholesterol, 18 NADP, 18 ADP, 18 Pi, 9 CO2
solubility of cholesterol
most insol substance
.2 mg/dL yet plasma conc is similar to blood glucose
structure of cholesterol
27 C's
4 rings
hydroxy at 3
circulation of cholesterol
synthed in liver
circulate in lipoproteins
-as chol esters
-usually with linoleic acid
cholesterol in membranes
100% in free (hydroxy) form

assoc w/sphingomyeline
cholesterol in bile
disposal
mostly free cholesterol
excretion of cholesterol
bile only
no enzyme to break rings
can't excrete in urine or breath
functions of cholesterol
membrane fluidity
-assoc w/sphingomyeline
-form rafts
-OH sticks out into interstit
bile salts
steroids
location of cholesterol production
all cells (except RBC)
cytoplasm (mostly ER)
especially liver
adrenal, testes, ovaries also
(pools of chol stored here)
intermediates in cholesterol synth
isoprenoid's

ubiquinone (mito ETC)
Dolichol (synth oligosacchs for GPs)
Farnesyl & geranyl (anchor fctn in memb proteins)

poss side effects for statins
cholesterol in brain
not cross BBB
mostly in glials
synthed in brain for brain use
convert to 24 hydroxy & sent to liver
24 hydroxylase
catabolic enzyme for cholesterol in liver
general rxn for Cholesterol synth
ACoA
HMG CoA
(HMG CoA reductase is rate limit)
mevalonic acid
PPMV
isoprenonyl
(geranyl)
(farnesyl)
...
cholesterol

25-30 rxns
first step cholesterol synth
move ACoA into cyto
via citrate
production of HMG CoA
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
fate of HMG CoA in cholesterol synthesis
gets reduced to mevalonic acid

HMG CoA reductase
rate limiting step
uses 2 NADPH
fate of mevalonic acid
kinase generates PPMV
uses LOTS of ATP

very high energy molecule
generation of isoprene molecules in cholesterol synth
decarboxylate PPMV
generation of geranyl in cholesterol
isomerise & condense Isoprene
uses 2 isoprenes
characteristics of geranyl
10C fatty acyl
high energy
put on proteins
increases hydrophobicity
characteristics of farnesyl
from geranyl
(from isoprenes)
changes protein characteristics
bisphosphanates
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)
regulation of cholesterol synthesis
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