[30.3] Free cholesterol can affect cholesterol metabolism in the body by
inhibiting cholesterol biosynthesis. The step at which free cholesterol
inhibits its biosynthesis is by inhibiting which of the following
A. Cyclizing of squalene to form lanosterol
B. Reduction of 7-dehydrocholesterol to form cholesterol
C. Formation of mevalonate from hydroxymethylglutaryl-CoA
D. Kinase that phosphorylates hydroxymethylglutaryl-CoA reductase
E. Condensation of acetyl-CoA and acetoacetyl-CoA to form
[30.4] A patient presents in your office with very high levels of serum cho-
lesterol. He states that he has tried to follow the diet and exercise reg-
imen you gave him last year. You decide that this patient would benefit
from a drug such as Lipitor (atorvastatin). This class of drugs is effec-
tive in treating hypercholesterolemia because it has what effect?
A. Stimulates phosphorylation of the P-hydroxy-P-methylglutaryl-
CoA reductase enzyme
B. Decreases the stability of the P-hydroxy-P-methylglutaryl-CoA
C. Binds cholesterol preventing it from being absorbed by the intestine
D. Directly prevents the deposition of cholesterol on artery walls
E. Inhibits the enzyme P-hydroxy-P-methylglutaryl-CoA reductase
A nsw ers
A. A common genetic mutation leading to high circulating LDL cho-
lesterol levels is caused by mutations in the LDL receptor. The lack
of a functional receptor prevents the removal of LDL cholesterol
from circulation. Apoprotein B-100 is found in the LDL-cholesterol
complex and is the protein recognized by the LDL receptor. In this
patient, the LDL receptor is normal so it is reasonable to conclude
that the reason that the LDL cholesterol remains in circulation is
because it is not recognized by the normal LDL receptor. A mutation
in the apoprotein B-100 such that it is not recognized by the receptor
would lead to elevated LDL-cholesterol levels.
B. The liver and intestine are the main sources of circulating lipids.
Chylomicrons carry triacylglycerides and cholesterol esters from the
intestine to other target tissues. VLDLs carry lipids from the liver into
circulation. Lipoproteins are a mix of lipids and specific proteins and
these complexes are classified based on their lipid/protein ratio.
Lipoprotein lipases degrade the triacylglycerides in the chylomicrons
and VLDLs with a concurrent release of apoproteins. This is a grad-
ual process which converts the VLDLs into IDLs and then LDLs.