Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the XDHgene.[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]
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]
^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. PMID8224915.
^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. PMID22678977. S2CID13495397.
Parzen SD, Fox AS (December 1964). "Purification of xanthine dehydrogenase from Drosophila melanogaster". Biochimica et Biophysica Acta (BBA) - Specialized Section on Enzymological Subjects. 92 (3): 465–471. doi:10.1016/0926-6569(64)90006-9. PMID14264879.
Parschat K, Canne C, Hüttermann J, Kappl R, Fetzner S (January 2001). "Xanthine dehydrogenase from Pseudomonas putida 86: specificity, oxidation-reduction potentials of its redox-active centers, and first EPR characterization". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1544 (1–2): 151–65. doi:10.1016/S0167-4838(00)00214-4. PMID11341925.
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. PMID8224915.
Hille R (November 1996). "The Mononuclear Molybdenum Enzymes". Chemical Reviews. 96 (7): 2757–2816. doi:10.1021/cr950061t. PMID11848841.
Meneshian A, Bulkley GB (July 2002). "The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction". Microcirculation. 9 (3): 161–75. doi:10.1038/sj.mn.7800136. PMID12080414. S2CID40739497.
Xu P, Zhu XL, Huecksteadt TP, Brothman AR, Hoidal JR (September 1994). "Assignment of human xanthine dehydrogenase gene to chromosome 2p22". Genomics. 23 (1): 289–91. doi:10.1006/geno.1994.1498. PMID7829092.
Minoshima S, Wang Y, Ichida K, Nishino T, Shimizu N (1994). "Mapping of the gene for human xanthine dehydrogenase (oxidase) (XDH) to band p23 of chromosome 2". Cytogenetics and Cell Genetics. 68 (1–2): 52–3. doi:10.1159/000133887. PMID7956358.
Rytkönen EM, Halila R, Laan M, Saksela M, Kallioniemi OP, Palotie A, Raivio KO (1994). "The human gene for xanthine dehydrogenase (XDH) is localized on chromosome band 2q22". Cytogenetics and Cell Genetics. 68 (1–2): 61–3. doi:10.1159/000133890. PMID7956361.
Xu P, Huecksteadt TP, Harrison R, Hoidal JR (March 1994). "Molecular cloning, tissue expression of human xanthine dehydrogenase". Biochemical and Biophysical Research Communications. 199 (2): 998–1004. doi:10.1006/bbrc.1994.1328. PMID8135849.
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. PMID8224915.
Satoh A, Sasago S, Takahashi S, Kato N (September 1993). "Regulation of xanthine dehydrogenase in rat liver in response to peroxisome proliferators". Biochemical and Biophysical Research Communications. 195 (2): 751–7. doi:10.1006/bbrc.1993.2109. PMID8373410.
Xu P, Huecksteadt TP, Hoidal JR (June 1996). "Molecular cloning and characterization of the human xanthine dehydrogenase gene (XDH)". Genomics. 34 (2): 173–80. doi:10.1006/geno.1996.0262. PMID8661045.
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. PMID8829220.
Rouquette M, Stevens C, Blake DR, Harrison R, Whish J, Whish WD (August 1997). "Expression of xanthine oxidase activity in human endothelial cells as a function of cell density". Biochemical Society Transactions. 25 (3): 532S. doi:10.1042/bst025532s. PMID9388748.
Newaz MA, Adeeb NN (March 1998). "Detection of xanthine oxidase in human plasma". The Medical Journal of Malaysia. 53 (1): 70–5. PMID10968141.
Frederiks WM, Vreeling-Sindelárová H (2002). "Ultrastructural localization of xanthine oxidoreductase activity in isolated rat liver cells". Acta Histochemica. 104 (1): 29–37. doi:10.1078/0065-1281-00629. PMID11993848.
Cejková J, Ardan T, Filipec M, Midelfart A (2003). "Xanthine oxidoreductase and xanthine oxidase in human cornea". Histology and Histopathology. 17 (3): 755–60. doi:10.14670/HH-17.755. PMID12168784.
External links
Overview of all the structural information available in the PDB for UniProt: P47989 (Xanthine dehydrogenase/oxidase) at the PDBe-KB.