Inosine monophosphate dehydrogenase

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Inosine monophosphate dehydrogenase
Inosine monophosphate dehydrogenase
Ribbon model of the inosine monophosphate dehydrogenase of Tritrichomonas fetus with inosine monophosphate (IMP) and MOA- bound, according to PDB  1MEH

Existing structural data : 1jcn , 1b3o , 1nf7 , 1nfb

Mass / length primary structure 514 amino acids
Secondary to quaternary structure Homotetramer
Cofactor potassium
Identifier
Gene name (s) IMPDH1 , IMPDH2
External IDs
Enzyme classification
EC, category 1.1.1.205 ,  oxidoreductase
Response type oxidation
Substrate IMP + NAD + + H 2 O
Products XMP + NADH / H +
Occurrence
Homology family IMPDH
Parent taxon Creature

Inosine monophosphate dehydrogenase (IMPDH) (also IMP dehydrogenase ) are enzymes that oxidize inosine monophosphate (IMP) to xanthosine monophosphate (XMP). This reaction step is indispensable and rate-determining for the biosynthesis of guanosine monophosphate (GMP), and thus of all guanosine nucleotides. IMPDH occur in all living things. In humans, there are two genes on chromosomes 7 and 3 that code for IMPDHs. Several isoforms of the gene product of IMPDH1 are known. It is localized in high concentrations in the retina . Mutations in IMPDH1 can lead to type 10 retinitis pigmentosa .

Catalyzed reaction

IMP+ NAD + + H 2 O ⇒ XMP+ NADH / H +

IMP is oxidized to XMP.

pharmacology

The IMPDH are targets for immunosuppressants ; they are inhibited , for example, by mycophenolic acid (MPA). Since the de novo synthesis of purines is essential for the proliferation of T and B lymphocytes , while other cell types can use the recycling metabolism, MPA has a stronger cytostatic effect on lymphocytes than on other cells, whereby these are selectively inhibited. That is why MPA is used as an immunosuppressant. There are variants of IMPDH that render MPA ineffective and whose carriers can therefore suffer rejection during transplants. Mutations in the IMPDH1 promoter can also lead to resistance to azathioprine .

Individual evidence

  1. ↑ UniProt P20839
  2. ↑ Bowne SJ, Liu Q, Sullivan LS, et al : Why do mutations in the ubiquitously expressed housekeeping gene IMPDH1 cause retina-specific photoreceptor degeneration? . In: Invest. Ophthalmol. Vis. Sci. . 47, No. 9, September 2006, pp. 3754-65. doi : 10.1167 / iovs.06-0207 . PMID 16936083 . PMC 2581456 (free full text).
  3. ↑ Wang J, Yang JW, Zeevi A, et al : IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients . In: Clin. Pharmacol. Ther. . 83, No. 5, May 2008, pp. 711-7. doi : 10.1038 / sj.clpt.6100347 . PMID 17851563 .
  4. ↑ Roberts RL, Gearry RB, Barclay ML, Kennedy MA: IMPDH1 promoter mutations in a patient exhibiting azathioprine resistance . In: The Pharmacogenomics Journal . 7, No. 5, October 2007, pp. 312-7. doi : 10.1038 / sj.tpj.6500421 . PMID 17001353 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Purine Metabolism  - Learning and Teaching Materials