Xanthine dehydrogenase

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

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)[1] Band 2p23.1 Start 31,334,321 bp[1] End 31,414,742 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 E2|17 45.25 cM Start 74,190,890 bp[2] End 74,257,191 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse Entrez 7498 22436 Ensembl ENSG00000158125 ENSMUSG00000024066 UniProt P47989 Q00519 RefSeq (mRNA) NM_000379 NM_011723 RefSeq (protein) NP_000370 NP_035853 Location (UCSC) Chr 2: 31.33 – 31.41 Mb Chr 17: 74.19 – 74.26 Mb PubMed search [3] [4]
Wikidata
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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
Search PMC articles PubMed articles NCBI proteins

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 ${\displaystyle \rightleftharpoons }$ 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]

See also

• Aldehyde oxidase and xanthine dehydrogenase, a/b hammerhead domain
• MOCOS
• Xanthine oxidase