Antimetabolites Reduce the Activities of Enzymes with Short Half-Lives in Addition to Inhibiting their Specific Targets

In evolution two pathways emerged for the biosynthesis of pyrimidine and purine nucleotides. The de novo biosynthetic pathway assembles nucleotides from small building blocks. By contrast, the salvage pathways provide mechanisms to recycle nucleosides and bases from the dead cells of tissues and from the blood stream1. In some lower organisms only one of these pathways operates2. However, in mammalians both de novo and salvage pathways function in all tissues. It has been recognized in the past 10 years that the activities of salvage enzymes in each of the biosynthetic segments of metabolism are markedly higher than those of the rate-limiting enzymes of de novo biosynthesis1.