Question

Enzymes generally make good drug targets because a specific reaction of interest can be targeted with a high degree of selectivity. Consider the following three drugs and explain why, although reaction-specific, the first two produce side effects, while the third does not.

A. Statins inhibit HMG CoA reductase to block intracellular cholesterol synthesis.
B. Methotrexate inhibits dihydrofolate reductase, which subsequently leads to blocked DNA replication.
C. Gleevec® inhibits BCR, a kinase that is only produced in certain types of leukemia cells.

Answer 1

While all enzymes can be targeted by drugs for specific reactions, drugs like Statins and Methotrexate affect broad biological processes, leading to side effects. Gleevec, however, targets an abnormal enzyme specific to certain leukemia cells, which is why it produces fewer side effects.

Step-by-step explanation:

Enzymes make good drug targets due to their specificity, but side effects can occur if they are not exclusive to a pathological condition. Statins inhibit HMG-CoA reductase, blocking cholesterol synthesis; however, because HMG-CoA reductase is expressed in various tissues, not just those related to the disease condition, there can be side effects due to interference with normal cellular functions. Methotrexate inhibits dihydrofolate reductase, affecting DNA replication. Its effects extend beyond cancer cells because this enzyme is also essential to normal cell function, leading to side effects. Conversely, Gleevec is highly specific, inhibiting BCR-ABL kinase produced only in certain leukemia cells, thus sparing other cells and leading to fewer side effects.