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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
Summary:
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
cholesterol biosynthesis.
Likely medication: HMG-CoA reductase inhibitor, otherwise known as
“statin” medications.
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
O bjectives
1.
Know about cholesterol metabolism.
2.
Understand the role of serum lipoproteins.
3.
Be aware of the types of hereditary hyperlipidemias.
4.
Know why the LDL level is increased with familial hypercholesterolemia.
D efinitions
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.
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