Xanthine dehydrogenase

PDB rendering based on 1fiq.

Available structures
PDB	2CKJ, 2E1Q

Identifiers

Symbols

XDH; XO; XOR

External IDs

OMIM: 607633 MGI: 98973 HomoloGene: 324 GeneCards: XDH Gene

EC number

1.17.1.4

Gene Ontology
Molecular function	• xanthine dehydrogenase activity • xanthine oxidase activity • xanthine oxidase activity • binding • iron ion binding • electron carrier activity • oxidoreductase activity • protein homodimerization activity • molybdopterin cofactor binding • metal ion binding • flavin adenine dinucleotide binding • 2 iron, 2 sulfur cluster binding
Cellular component	• extracellular region • cytoplasm • peroxisome • cytosol
Biological process	• purine base metabolic process • purine nucleotide catabolic process • lactation • xanthine catabolic process • regulation of epithelial cell differentiation • nucleobase, nucleoside and nucleotide metabolic process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
31.56 – 31.64 Mb

Chr 17:
74.23 – 74.3 Mb

PubMed search

[1]

[2]

xanthine dehydrogenase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles

Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the XDH gene.^[1]^[2]

1 Function
2 Clinical significance
3 See also
4 References
5 Further reading

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:

xanthine + NAD⁺ + H₂O $\rightleftharpoons$ 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 belongs to the family of oxidoreductases, to be specific, those acting on CH or CH2 group 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. This enzyme participates in purine metabolism.

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]

References

^ ^a ^b ^c "Entrez Gene: XDH xanthine dehydrogenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7498.
^ 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): 279–84. doi:10.1016/0378-1119(93)90652-J. PMID 8224915.

Battelli MG, Lorenzoni E (1982). "Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver". Biochem. J. 207 (1): 133–8. PMC 1153833. PMID 6960894. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1153833.
Corte ED, Stirpe F (1972). "The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme". Biochem. J. 126 (3): 739–45. PMC 1178433. PMID 4342395. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1178433.
PARZEN SD, FOX AS (1964). "PURIFICATION OF XANTHINE DEHYDROGENASE FROM DROSOPHILA MELANOGASTER". Biochim. Biophys. Acta. 92: 465–71. PMID 14264879.
Rajagopalan KV, Handler P (1967). "Purification and properties of chicken liver xanthine dehydrogenase". J. Biol. Chem. 242 (18): 4097–107. PMID 4294045.
Smith ST, Rajagopalan KV, Handler P (1967). "Purification and properties of xanthine dehydroganase from Micrococcus lactilyticus". J. Biol. Chem. 242 (18): 4108–17. PMID 6061702.
Parschat K, Canne C, Huttermann J, Kappl R, Fetzner S (2001). "Xanthine dehydrogenase from Pseudomonas putida 86: specificity, oxidation-reduction potentials of its redox-active centers, and first EPR characterization". Biochim. Biophys. Acta. 1544 (1–2): 151–65. doi:10.1016/S0167-4838(00)00214-4. PMID 11341925.
N, Nishino T; Amaya, Y; Noda, K; Minoshima, S; Hosoya, T; Sakai, O; Shimizu, N; Nishino, T (1993). "Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene". Gene. 133 (2): 279–84. doi:10.1016/0378-1119(93)90652-J. PMID 8224915.
Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF (2000). "Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: Structure-based mechanism of conversion". Proc. Natl. Acad. Sci. U. S. A. 97 (20): 10723–8. doi:10.1073/pnas.97.20.10723. PMC 27090. PMID 11005854. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27090.
C; Theis, K; Leimkühler, S; Rappa, R; Rajagopalan, KV; Kisker, C (Camb). "Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus". S Structure. (1): 115–25. PMID 11796116.
Hille R (1996). "The Mononuclear Molybdenum Enzymes". Chem. Rev. 96 (7): 2757–2816. doi:10.1021/cr950061t. PMID 11848841.

Meneshian A, Bulkley GB (2002). "The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction". Microcirculation (New York, N.Y. : 1994) 9 (3): 161–75. doi:10.1038/sj.mn.7800136. PMID 12080414.
Xu P, Huecksteadt TP, Harrison R, Hoidal JR (1995). "Molecular cloning, tissue expression of human xanthine dehydrogenase". Biochem. Biophys. Res. Commun. 215 (1): 429. doi:10.1006/bbrc.1995.2482. PMID 7575623.
Xu P, Zhu XL, Huecksteadt TP et al. (1995). "Assignment of human xanthine dehydrogenase gene to chromosome 2p22". Genomics 23 (1): 289–91. doi:10.1006/geno.1994.1498. PMID 7829092.
Minoshima S, Wang Y, Ichida K et al. (1994). "Mapping of the gene for human xanthine dehydrogenase (oxidase) (XDH) to band p23 of chromosome 2". Cytogenet. Cell Genet. 68 (1–2): 52–3. doi:10.1159/000133887. PMID 7956358.
Rytkönen EM, Halila R, Laan M et al. (1994). "The human gene for xanthine dehydrogenase (XDH) is localized on chromosome band 2q22". Cytogenet. Cell Genet. 68 (1–2): 61–3. doi:10.1159/000133890. PMID 7956361.
Xu P, Huecksteadt TP, Harrison R, Hoidal JR (1994). "Molecular cloning, tissue expression of human xanthine dehydrogenase". Biochem. Biophys. Res. Commun. 199 (2): 998–1004. doi:10.1006/bbrc.1994.1328. PMID 8135849.
Ichida K, Amaya Y, Noda K et al. (1993). "Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene". Gene 133 (2): 279–84. doi:10.1016/0378-1119(93)90652-J. PMID 8224915.
Satoh A, Sasago S, Takahashi S, Kato N (1993). "Regulation of xanthine dehydrogenase in rat liver in response to peroxisome proliferators". Biochem. Biophys. Res. Commun. 195 (2): 751–7. doi:10.1006/bbrc.1993.2109. PMID 8373410.
Xu P, Huecksteadt TP, Hoidal JR (1997). "Molecular cloning and characterization of the human xanthine dehydrogenase gene (XDH)". Genomics 34 (2): 173–80. doi:10.1006/geno.1996.0262. PMID 8661045.
Saksela M, Raivio KO (1996). "Cloning and expression in vitro of human xanthine dehydrogenase/oxidase". Biochem. J. 315 ( Pt 1) (Pt 1): 235–9. PMC 1217176. PMID 8670112. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1217176.
Many A, Westerhausen-Larson A, Kanbour-Shakir A, Roberts JM (1996). "Xanthine oxidase/dehydrogenase is present in human placenta". Placenta 17 (5–6): 361–5. doi:10.1016/S0143-4004(96)90061-2. PMID 8829220.
Hellsten Y, Frandsen U, Orthenblad N et al. (1997). "Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation". J. Physiol. (Lond.) 498 ( Pt 1) (Pt 1): 239–48. PMC 1159248. PMID 9023782. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1159248.
Ichida K, Amaya Y, Kamatani N et al. (1997). "Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria". J. Clin. Invest. 99 (10): 2391–7. doi:10.1172/JCI119421. PMC 508078. PMID 9153281. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=508078.
Rouquette M, Stevens C, Blake DR et al. (1998). "Expression of xanthine oxidase activity in human endothelial cells as a function of cell density". Biochem. Soc. Trans. 25 (3): 532S. PMID 9388748.
Newaz MA, Adeeb NN (2000). "Detection of xanthine oxidase in human plasma". Med. J. Malaysia 53 (1): 70–5. PMID 10968141.
Martelin E, Palvimo JJ, Lapatto R, Raivio KO (2000). "Nuclear factor Y activates the human xanthine oxidoreductase gene promoter". FEBS Lett. 480 (2–3): 84–8. doi:10.1016/S0014-5793(00)01909-8. PMID 11034305.
Stiborová M, Frei E, Sopko B et al. (2002). "Carcinogenic aristolochic acids upon activation by DT-diaphorase form adducts found in DNA of patients with Chinese herbs nephropathy". Carcinogenesis 23 (4): 617–25. doi:10.1093/carcin/23.4.617. PMID 11960915.
Frederiks WM, Vreeling-Sindelárová H (2002). "Ultrastructural localization of xanthine oxidoreductase activity in isolated rat liver cells". Acta Histochem. 104 (1): 29–37. doi:10.1078/0065-1281-00629. PMID 11993848.
Cejková J, Ardan T, Filipec M, Midelfart A (2003). "Xanthine oxidoreductase and xanthine oxidase in human cornea". Histol. Histopathol. 17 (3): 755–60. PMID 12168784.

PDB gallery

1fiq: CRYSTAL STRUCTURE OF XANTHINE OXIDASE FROM BOVINE MILK

1wyg: Crystal Structure of a Rat Xanthine Dehydrogenase Triple Mutant (C535A, C992R and C1324S)

2ckj: HUMAN MILK XANTHINE OXIDOREDUCTASE

Xanthine dehydrogenase

Contents

Function

Clinical significance

See also

References

Further reading