CLINICAL CASES
315
1,25-Dihydroxycholecalciferol
Figure 34-3. Biosynthesis of active vitamin D3.
requires reactions that occur in the liver and kidneys and acts in a manner sim-
ilar to steroid hormones to activate transcription, thereby regulating gene
expression.
Lovastatin is a member of a class of drugs (atorvastatin and simvastatin are
others in this class) called statins that are used to treat hypercholesterolemia.
The statins act as competitive inhibitors of the enzyme HMG-CoA reduc-
tase. These molecules mimic the structure of the normal substrate of the
enzyme (HMG-CoA) and act as transition state analogues. While the statins
are bound to the enzyme, HMG-CoA cannot be converted to mevalonic acid,
thus inhibiting the whole cholesterol biosynthetic process. Recent studies indi-
cate that there may be important secondary effects of statin therapy because
some of the medical benefits of statins are too rapid to be a result of decreas-
ing atherosclerotic lesions. Statin therapy has been associated with reduced
risks of dementia, Alzheimer disease, ischemic cerebral stroke, and other dis-
eases that are not correlated with high cholesterol levels. Although this is still
an active area of research, it appears that the pleiotropic effects of statins may
be a result of a reduction in the synthesis of isoprenoid intermediates that are
formed in the pathway of cholesterol biosynthesis.
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