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.