Chemistry Reference
In-Depth Information
medications. Many people have high cholesterol and cholesterol medication
is near the top of many lists of the top drugs. Similarly, hypertension afflicts
about one third of the population and often requires more than one type of
medication. Proton pump inhibitors are used for the treatment of ulcers, heart-
burn and other symptoms of gastroesophageal reflux disease which afflicts
about 10 - 20% of the population. An increasing number of people are devel-
oping diabetes, the seventh leading cause of death in the U.S. and there are
several medications prescribed for diabetics. The last area chosen, antidepres-
sants, affects about 10% of the population.
11.2 CHOLESTEROL DRUGS
Cardiovascular disease accounts for more deaths, about 30% globally, than
any other disease and the over-accumulation of cholesterol is known to play
a central role in cardiovascular disease [7]. In the United States population
older than 19, 15% have cholesterol levels higher than 240 mg/dL [8].
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase) con-
verts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of
cholesterol. Human 3-hydroxy-3-methylglutaryl coenzyme A, also abbre-
viated as HMGR consists of a polypeptide chain of 888 amino acids [9].
Acetyl-CoA condenses with acetoacetyl-CoA to form HMG-CoA reductase.
O
OH
O
O
O
O
H
2
O
+ HS-CoA
+
−
O
S
CoA
S
CoA
S
CoA
Acetyl CoA
Acetoacetyl CoA
HMG-CoA
Hydride transfer from NADPH (the reduced form of nicotinamide ade-
nine dinucleotide phosphate) gives initially mevaldyl-CoA which then forms
mevaldehyde. Another reduction with NADPH gives mevalonate.
OH
O
−
O
OH
O
O
NADPH
−
CoA-SH
−
O
S
CoA
−
O
S
CoA
HMG-CoA
Mevaldyl-CoA
O
OH
O
OH
O
NADPH
CH
2
OH
−
O
H
−
O
Mevalonate
Mevaldehyde
Mevalonate is converted in a series of biosynthetic steps to squalene which
in turn is converted to cholesterol.
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