Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
19 Cards in this Set
- Front
- Back
|
what are the main functions of cholesterol?
|
modulates fluidity of cell membrane
precursors of bio active compounds like steroid hormones, vitamin D, bile acids (emulsifies lipids, assists with digestion and absorption) |
|
|
what are the sources of cholesterol?
|
50% from diet
synthesized de novo, mainly by liver, intestine, adrenal cortex & reproductive tissues |
|
|
what is the structure of cholesterol?
|
steroid skeleton (4 rinks)
almost completely saturated (1 double bond) ring structure almost planar one OH (hydroxyl group) > esterification |
|
|
whatt is the major compound produced from cholesterol?
|
bile acids
|
|
|
what is the starting point of cholesterol synthesis? where does it come from?
|
acetyl co A
sources: B oxidation of FAs dehydrogennation of pyruvate oxidation of ketogenic amino acids |
|
|
where does cholesterol synthesis occur?
|
cytosol
although some enzymes in ER |
|
|
Where does the energy for cholesterol synthesis come from?
|
NADPH (reducing power)
ATP |
|
|
What is the first step of cholesterol synthesis?
|
3 acetyl coA --HMG CoA Synthase-> HMG CoA --HMG CoA Reductase--> Mevalonate
the synthesis of mevalonate is the committed step **rate limiting step HMG CoA Synthase is reversible, Reductase is NOT |
|
|
What is the short term regulation of HMG CoA reductase?
|
inhibited by phosphorylation (low atp > AMPK, glucagon promote)
activated by dephosphorylation (insulin activates phosphatase) high cholesterol > proteolytic degradation of HMG CoA |
|
|
What are longer term regulation of HMG CoA Redcutase
|
transcriptional control (SREBP - sterol regulatory element binding protein) binds to sterol regulatory element (SRE) and activates transcription of reductase gene)
high cholesterol prevents cleavage >no activation HMG CoA Reductase > not active low cholesterol > SREBP translocates to Golgi from ER > cleaved > goes to nucleus > activates transcription of HMG CoA reductase gene |
|
|
How and where are cholesterol esters synthesized?
|
In most cells
with enzyme ACAT (acyl CoA cholesterol acyltransferase) once esterified, can be packaged into chylomycrons (main way to transport) and this is imporant to keep the free level of cholesterol low |
|
|
What do statin drugs inhibit?
|
HMG CoA reductase
studies show is decreases LDL by 20-60% |
|
|
What rhythm does cholesterol biosynthesis show? When is it best to take statin drugs?
|
circadian rhythm = peaks 6 hrs after dark, minimum 6 hours after light exposure
correlates with HMG CoA reductase so best to take statins at night to maximize their effect |
|
|
How is cholesterol excreted?
|
sterol ring cant be degraded so mostly excreted as biliary cholesterol or as bile acids (which are reabsorbed by gut = enterohepatic circulation)
|
|
|
Why are bile acid sequestrants so important?
|
bile acid sequestrants lower cholesterol by preventing reabsorption of bile acids in the gut so they can be excreted in feces
> lower cholesterol (also lose some essential vitamins) |
|
|
where are bile acids made? What catalyzes the RLS?
|
liver
7a-hydroxylase (inhibited by bile acids - end product) |
|
|
what does bile contain?
|
bile acids
cholesterol lipids billirubin |
|
|
How are bile acids conjugated?
|
with glycine or taurine
> bile acids in GI can be altered by bacteria > secondary bile acids > reabsorbed and returned to liver |
|
|
How does cholesterol produce gall stones?
|
phospholipids maintain cholesterol solubility, must be in 1:1 ratio
if greater > cholesterol crystallizes > increased frequency of gall bladder contraction > gall stones |
