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CASE FILES: BIOCHEMISTRY
The disease
familial hypercholesterolemia
results from a mutation in the
LDL-receptor gene found on chromosome 19. The overall phenotype of the
inability to internalize the LDL receptor can be caused by three different types
of defects. In the first type, the LDL receptor is not produced. The second type
is a result of a mutation in the terminal region of the receptor that results in an
LDL receptor unable to bind LDL. The third type is caused by a mutation in
the C-terminal region that prevents the LDL-receptor complex from undergo-
ing endocytosis. In the absence of a functioning LDL receptor, LDL choles-
terol levels are greatly elevated in individuals with this disease. This elevation
results in premature atherosclerosis of the coronary arteries. Genetic defects in
apoprotein B-100, the protein in the LDL recognized by the LDL receptor,
also exist and lead to elevated LDL because the LDL complex is not recog-
nized by the LDL receptor. A diet low in fat and cholesterol, an exercise regi-
men, and anticholesterol medications are used in the treatment of this disease.
C O M P R E H E N SIO N Q U E ST IO N S
[30.1] A patient presents in your office with very high levels of serum cho-
lesterol. After a series of tests, you conclude that the patient has high
circulating levels of LDL cholesterol, but has normal levels of the liver
LDL receptor. One possible explanation for this observation is which
of the following?
A. The patient has a mutated form of apoprotein B-100.
B. The inability to selectively remove cholesterol from the LDL
complex.
C. The absence of the enzyme lipoprotein lipase.
D. Decreased levels of acyl-CoA: cholesterol acyltransferase.
E. Altered phosphorylation of the LDL receptor.
[30.2] A patient with hereditary type I hyperlipidemia presents with elevated
levels of chylomicrons and VLDL triglycerides in the blood. The main
function of the chylomicrons in circulation is to do which of the
following?
A. Transport lipids from the liver
B. Transport dietary lipids from the intestine to target tissues
C. Transport cholesterol from IDL to LDL
D. Act as a receptor for triacylglycerols in the liver
E. Bind cholesterol esters exclusively
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