Answer to Question #165559 in Cell Biology for Prince

Question #165559

you could describe the mechanism of drugs such as the statins, which inhibit the function of the enzyme HMG-CoA reductase and so reduce the synthesis of cholesterol in the body. You could report the manner in which the inhibitors interact with their enzyme target, if they are allosteric or competitive and what the result of that inhibition is to the cell. (Try to pick an alternative example to statins).

Expert's answer

The beneficial effects of statins are the result of their capacity to reduce cholesterol biosynthesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Statins have antiatherosclerotic effects, that positively correlate with the percent decrease in LDL cholesterol. In addition, they can exert antiatherosclerotic effects independently of their hypolipidemic action. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, HMG-CoA reductase inhibition has beneficial pleiotropic effects. Consequently, statins reduce significantly the incidence of coronary events, both in primary and secondary prevention, being the most efficient hypolipidemic compounds that have reduced the rate of mortality in coronary patients. Independent of their hypolipidemic properties, statins interfere with events involved in bone formation and impede tumor cell growth.

Statins work by competitively blocking the active site of the first and key rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase. Inhibition of this site prevents substrate access, thereby blocking the conversion of HMG-CoA to mevalonic acid.

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