Cholesterol Biosynthesis (Homo sapiens) - WikiPathways
Cholesterol biosynthesis (Homo sapiens) - WikiPathways
Lovastatin is an inhibitor of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme which catalyzes the conversion of HMG-CoA to mevalonate. Mevalonate is a required building block for cholesterol biosynthesis and lovastatin interferes with its production by acting as a reversible competitive inhibitor for HMG-CoA which binds to the HMG-CoA reductase. Lovastatin, being inactive in the native form, the form in which it is administered,is hydrolysed to the β-hydroxy acid form in the body and it is this form which is active.
× WikiPathways Pathway Cholesterol Biosynthesis
It is now generally accepted that a major risk factor for the development of coronary heart disease is an elevated concentration of plasma cholesterol, especially (LDL) cholesterol. The objective is to decrease excess levels of cholesterol to an amount consistent with maintenance of normal body function. Cholesterol is biosynthesized in a series of more than 25 separate enzymatic reactions that initially involves 3 successive condensations of acetyl-CoA units to form a 6-carbon compound, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA). This is reduced to mevalonate and then converted in a series of reactions to the isoprenes that are building blocks of squalene, the immediate precursor to sterols, which cyclizes to lanosterol (a methylated sterol) and further metabolized to cholesterol. A number of early attempts to block the synthesis of cholesterol resulted in agents that inhibited late in the biosynthetic pathway between lanosterol and cholesterol. A major rate limiting step in the pathway is at the level of the microsomal enzyme which catalyzes the conversion of HMG CoA to mevalonic acid and which has been considered to be a prime target for pharmacologic intervention for several years.
Cholesterol: Synthesis, Metabolism, Regulation
Given the well-recognized role of cholesterol in cardiovascular disease, it is surprising that some studies have shown an inverse correlation between cholesterol levels and mortality. A 2009 study of patients with acute coronary syndromes found an association of hypercholesterolemia with better mortality outcomes.. In the , in subjects over 50 years of age they found an 11% increase overall and 14% increase in CVD mortality per 1 mg/dL per year drop in total cholesterol levels. The researchers attributed this phenomenon to the fact that people with severe chronic diseases or cancer tend to have below-normal cholesterol levels. This explanation is not supported by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all ages and women over 50 with very low cholesterol were increasingly likely to die of cancer, liver diseases, and mental diseases. This result indicates that the low-cholesterol effect occurs even among younger respondents, contradicting the previous assessment among cohorts of older people that this is a proxy or marker for frailty occurring with age.