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xanthine dehydrogenase
xanthine dehydrogenase
	Bos taurus
Identifiers
EC no.	1.17.1.4
CAS no.	9054-84-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
PMC
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PMC	articles
PubMed	articles
NCBI	proteins

XDH
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2CKJ, 2E1Q
Identifiers
Aliases	XDH, XO, XOR, xanthine dehydrogenase, XAN1
External IDs	OMIM: 607633; MGI: 98973; HomoloGene: 324; GeneCards: XDH; OMA:XDH - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	31,414,742 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	74,257,191 bp
RNA expression pattern
	Top expressed in
	jejunal mucosa; ; mucosa of ileum; ; palpebral conjunctiva; ; mucosa of colon; ; mucosa of sigmoid colon; ; duodenum; ; liver; ; right lobe of liver; ; nasal epithelium; ; tail of epididymis;
	Top expressed in
	granulocyte; ; duodenum; ; stroma of bone marrow; ; jejunum; ; decidua; ; ankle joint; ; white adipose tissue; ; gastrula; ; esophagus; ; left lobe of liver;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	iron ion binding; protein homodimerization activity; xanthine oxidase activity; flavin adenine dinucleotide binding; oxidoreductase activity, acting on CH-OH group of donors; iron-sulfur cluster binding; metal ion binding; catalytic activity; molybdopterin cofactor binding; electron transfer activity; xanthine dehydrogenase activity; oxidoreductase activity; 2 iron, 2 sulfur cluster binding; oxidoreductase activity, acting on the aldehyde or oxo group of donors; FAD binding;
Cellular component	cytoplasm; cytosol; peroxisome; sarcoplasmic reticulum; extracellular region; extracellular space;
Biological process	positive regulation of p38MAPK cascade; negative regulation of protein phosphorylation; negative regulation of protein kinase B signaling; purine nucleotide catabolic process; negative regulation of endothelial cell differentiation; negative regulation of gene expression; negative regulation of endothelial cell proliferation; positive regulation of reactive oxygen species metabolic process; negative regulation of vasculogenesis; negative regulation of vascular endothelial growth factor signaling pathway; lactation; regulation of epithelial cell differentiation; xanthine catabolic process; activation of cysteine-type endopeptidase activity involved in apoptotic process; electron transport chain;
	Sources:Amigo / QuickGO
Orthologs
	7498
	22436
	ENSG00000158125
	ENSMUSG00000024066
	P47989
	Q00519
	NM_000379
	NM_011723
	NP_000370
	NP_035853
	Wikidata
View/Edit Human	View/Edit Mouse

Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the XDH gene.^[5]^[6]

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.^[5]

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 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.^[5] It has been shown that patients with lung adenocarcinoma tumors which have high levels of XDH gene expression have lower survivals.^[7]^[8] Addiction to XDH protein has been used to target NSCLC tumors and cell lines in a precision oncology manner.^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000158125 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024066 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "Entrez Gene: XDH xanthine dehydrogenase". Retrieved October 25, 2012.
^ 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.
^ 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.
^ ^a ^b 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.

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