Inosine 5′-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo synthesis of guanine nucleotides and is positioned at the branch point between adenine and guanine biosynthesis. It is also strategically positioned in the metabolic pathway of thiopurines. IMPDH is considered to be the rate-limiting enzyme in the metabolism of thiopurine drugs to 6-thioguanine nucleotides (6-TGNs) (Leyva et al. 1976). IMPDH dehydrogenates 6-thioinosine 5’-monophosphate (6TIMP) to 6-thioxanthosine 5'-monophosphate (6TXMP), an intermediate metabolite in the formation of 6-TGNs.
IMP dehydrogenase activity of IMPDH tetramers [cytosol]