CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 30:
H Y P E R C H O L E ST E R O L IN E M IA
A 48-year-old male with strong family history of heart disease and
now angina and exertional dyspnea presents with a significantly elevated cho-
lesterol level. A medication is prescribed that is directed at the rate-limiting
step of cholesterol biosynthesis.
Rate-limiting step: The enzyme hydroxymethylglutaryl-CoA reductase
(HMG-CoA reductase) catalyzes an early rate-limiting step in
Likely medication: HMG-CoA reductase inhibitor, otherwise known as
C L IN IC A L C O R R E L A T IO N
Hyperlipidemia is one of the most treatable risk factors of atherosclerotic vas-
cular disease. In particular, the level of the low-density lipoprotein (LDL) cor-
relates with the pathogenesis of atherosclerosis. Exercise, dietary adjustments,
and weight loss are the initial therapy of hyperlipidemia. If these are not suf-
ficient, then pharmacologic therapy is required. The exact LDL targets depend
on the patient’s risk of cardiovascular disease. For example, if an individual
has had a cardiovascular event previously (heart attack or stroke), the LDL tar-
get is 100 mg/dL; 1 to 2 risk factors without prior events = 130 mg/dL; and no
risk factors = 160 mg/dL.
A PPR O A C H TO L IP ID M E T A B O L ISM
Know about cholesterol metabolism.
Understand the role of serum lipoproteins.
Be aware of the types of hereditary hyperlipidemias.
Know why the LDL level is increased with familial hypercholesterolemia.
Apolipoprotein: The protein component of a lipoprotein; in addition to
being a structural component of a lipoprotein, apolipoproteins also serve
as activators of enzymes and ligands for receptors.
Chylomicron: A lipoprotein synthesized by the intestine to transport
dietary lipids to peripheral tissues and the liver.