IMP dehydrogenase

Inosine monophosphate dehydrogenase ( IMPDH ) (also IMP dehydrogenase ) are called enzymes inosine monophosphate (IMP ) to Xanthosinmonophosphat (XMP ) oxidize. This reaction step is indispensable and the rate-determining for the biosynthesis of guanosine monophosphate ( GMP), and hence of all guanosine nucleotides. IMPDH are present in all living things. In humans, there are two genes that code for IMPDH. From the gene product of IMPDH1 several isoforms are known. It is located in a high concentration in the retina. Mutations in IMPDH1 can lead to retinitis pigmentosa type 10.

Catalyzed reaction

NAD H2O ⇒ NADH / H

IMP is oxidized to XMP.

Pharmacology

The IMPDH are targets for immunosuppressive drugs; they are inhibited, for example by mycophenolic acid (MPA ). As for the proliferation of T and B lymphocytes in the de novo synthesis of purines, whereas other cell types can utilize salvage pathways, MPA has more potent cytostatic effects on lymphocytes than on other cells, making them selectively inhibited. Therefore, MPA is used as an immunosuppressant. There are variants of IMPDH, make the MPA ineffective and their carriers can therefore suffer rejection in transplants. Mutations at IMPDH1 promoter can equally lead to azathioprine for resistance.

Xanthosine monophosphate Protein isoform Digital Object Identifier PubMed Central Clinical Pharmacology & Therapeutics
410424
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