Lipoproteins Flashcards
Friedewald equation (mg/dl)
LDL = total cholesterol - HDL - (total triglycerides/5)
Most plasma cholesterol is in ______ form.
esterifeid.
Fatty acid attached at C3: makes structure more hydrophobic
How are cholesterol and its esters transported?
in association with a protein as a component of a lipoprotein particle
or
solubilized by phospholipids and bile salts in bile
What is a chylomicron?
lipoprotein particle derived from the intestine;
part of exogenous pathway of lipoprotein metapolism
NB: source of liver cholesterol is from diet (via chylomicron remnants)
What is the lipoprotein particle derived from the liver?
Which pathway of lipoprotein metabolism?
- VLDL
- endogenous pathway
What is liver’s role with cholesterol?
- central!
- Sources: diet (chylomicron remnants); local synthesis; extrahepatic tissues (via HDL and LDL)
Liver export cholesterol:
1) in VDL
2) excretes it in bile
3) converts it to bile salts
Where does cholesterol synthesis take place?
cytosol of virtually all cell types
De novo: liver and intestine
Name the following key factor in cholesterol synthesis
-source for carbon atoms:
Acetyl-CoA
Name the following key factor in cholesterol synthesis:
-major co-factor
2 NADPH
Name the following key factor in cholesterol synthesis:
-catalyzing enzyme of the regulated step
HMG-CoA reductase
Name the following key factor in cholesterol synthesis:
-product of the committed step
Mevalonate (5 carbons)
Is ATP consumed in making mevalonate?
the committed step
Yes
What is the committed step (what to what, how)?
HMG-CoA –> Mevalonate
- catalyzed by HMG-CoA Reductase
- using 2 NADPH as a cofactor
- consuming ATP
What does mevalonic acid give rise to?
a) squalene –> lanosterol –> cholesterol
b) terpenes (isopreniods/isoprenes): farnesyl pyrophosphate, dolichol, ubiquinones, geranylgeranyl pyrophosphate
Which products of mevalonic acid can be conjugated with proteins and then serve as lipid anchors?
farnesyl pyrophosphate
geranylgeranyl pyrophosphate
What is the role of dolichol pyrophosphate?
(dolichol is a product of mevalonic acid)
required for the dolichol pathway of N-linked posttranslational protein glycolsylation
What is the role of ubiquinones?
product of mevalonic acid
ubiquinones can be reduced to ubiquinols, which can donate electrons to ETC as part of oxphos
What are 2 enzymes required for esterification of cholesterol?
1) ACAT
2) LCAT
What is the purpose of esterification of cholesterol?
cholesterol esters are more hydrophobic than cholesterol, enabling them to be packaged, stored, and transported easily
(therefore cannot be incorporated into membranes or transported through them nakedly)
Where are cholesterol esters found?
hepatocytes and steroid cells
(stored in lipid droplets in cytosol)
NB: most ofter cells contain virtually no cholesterol esters
Where does ACAT work?
epithelial cells of small intestine and in liver
Where does LCAT work?
blood: LCAT bound to HDL
uses FA from phospholipid lecithin on peripheral cell to esterify cholesterol to cholesterol esters, which are stored in HDL
How does cholesterol act to control de novo cholesterol synthesis?
1) stimulates proteolysis of HMG CoA reductase (neg fb)
2) regulates expression of HMG-COA reductase gene by influencing RNA pol II’s rate of HMG-CoA reductase mRNA synthesis
What is the effect of insulin on HMG-CoA reductase (HMGR)?
stimulates
indicating glucose abundant and therefore signal of growth and anabolism
