312
CASE FILES: BIOCHEMISTRY
A N S W E R TO C A SE 34: STATIN M E D IC A T IO N S
Summary:
A 49-year-old female with history of elevated cholesterol on lovas-
tatin, which appears to be improving serum cholesterol levels.
Mechanism action of lovastatin: P-Hydroxy-P-methylglutaryl-coenzyme
A (HMG-CoA) reductase inhibitor.
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 coronary heart dis-
ease. Initially, when the fasting low-density lipoprotein (LDL) cholesterol is
measured and found to be elevated, life style modification is recommended
such as dietary adjustments, exercise, and weight loss. The lipids are measured
again after a 3- to 6-month interval. If the LDL cholesterol level is again found
to be above threshold, then pharmacologic therapy is entertained. One of the
most common medications is a statin agent, acting to inhibit HMG-CoA
reductase. The potential side effects include elevated liver function tests,
increased muscle creatine phosphokinase (CPK) secondary to myopathy and
rarely rhabdomyolysis. Other agents that may be considered include bile acid
sequestrants, nicotinic acid, fibric acid, and fish oils.
A PPR O A C H TO C H O L E ST E R O L SY N T H E SIS
O bjectives
1.
Know about the role of HMG-CoA reductase in cholesterol synthesis.
2.
Know the mechanism of action of statin medications.
3.
Understand the role of cholesterol on steroid synthesis.
4.
Be aware that niacin decreases lipolysis in adipose tissue and very-
low-density lipoprotein (VLDL) synthesis in liver.
D efinitions
Cytochrome P450 enzyme system: The cytochromes P450 are mixed-
function oxidases that require both NADPH and O2. They are involved
in a number of reactions in the conversion of lanosterol to cholesterol, as
well as important steps in the synthesis of steroid hormones. Cytochromes
P450 are very important in the detoxification of xenobiotics and in the
metabolism of drugs.
HMG-CoA reductase: P-Hydroxy-P-methylglutaryl-CoA reductase; the
enzyme that catalyzes the rate-limiting and committed step in the syn-
thesis of cholesterol. It converts P-hydroxy-P-methylglutaryl-CoA
(HMG-CoA) to mevalonate.
previous page 326 Case Files   Biochemistry read online next page 328 Case Files   Biochemistry read online Home Toggle text on/off