Xanthine dehydrogenase

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xanthine dehydrogenase
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EC no.1.17.1.4
CAS no.9054-84-6
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Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the XDH gene.[1][2]

Function

Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The enzyme is a homodimer. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification.[1] Xanthine dehydrogenase catalyzes the following chemical reaction:

File:Xanthine dehydrogenase.svg
xanthine + NAD+ + H2O urate + NADH + H+

The three substrates of this enzyme are xanthine, NAD+, and H2O, whereas its three products are urate, NADH, and H+. This enzyme participates in purine metabolism.

Nomenclature

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on CH or CH2 groups with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is xanthine:NAD+ oxidoreductase. Other names in common use include NAD+-xanthine dehydrogenase, xanthine-NAD+ oxidoreductase, xanthine/NAD+ oxidoreductase, and xanthine oxidoreductase.

Clinical significance

Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism.[1] It has been shown that patients with lung adenocarcinoma tumors which have high levels of XDH gene expression have lower survivals.[3][4] Addiction to XDH protein has been used to target NSCLC tumors and cell lines in a precision oncology manner.[4]

See also

References

  1. 1.0 1.1 1.2 "Entrez Gene: XDH xanthine dehydrogenase". Retrieved October 25, 2012.
  2. Ichida K, Amaya Y, Noda K, Minoshima S, Hosoya T, Sakai O, Shimizu N, Nishino T (November 1993). "Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene". Gene. 133 (2): 279–284. doi:10.1016/0378-1119(93)90652-J. PMID 8224915.
  3. Konno H, Minamiya Y, Saito H, Imai K, Kawaharada Y, Motoyama S, Ogawa J (October 2012). "Acquired xanthine dehydrogenase expression shortens survival in patients with resected adenocarcinoma of lung". Tumour Biology. 33 (5): 1727–1732. doi:10.1007/s13277-012-0431-2. PMID 22678977. S2CID 13495397.
  4. 4.0 4.1 Tavassoly I, Hu Y, Zhao S, Mariottini C, Boran A, Chen Y, Li L, Tolentino RE, Jayaraman G, Goldfarb J, Gallo J, Iyengar R (May 2019). "Genomic signatures defining responsiveness to allopurinol and combination therapy for lung cancer identified by systems therapeutics analyses". Molecular Oncology. 13 (8): 1725–1743. doi:10.1002/1878-0261.12521. PMC 6670022. PMID 31116490.

Further reading

External links

  • Overview of all the structural information available in the PDB for UniProt: P47989 (Xanthine dehydrogenase/oxidase) at the PDBe-KB.