Xanthine dehydrogenase

Last updated
XDH
Protein XDH PDB 1fiq.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases XDH , XO, XOR, xanthine dehydrogenase, XAN1
External IDs OMIM: 607633; MGI: 98973; HomoloGene: 324; GeneCards: XDH; OMA:XDH - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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
View/Edit Human View/Edit Mouse
xanthine dehydrogenase
1fo4.jpg
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

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

Contents

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 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. [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

Related Research Articles

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.

<span class="mw-page-title-main">Xanthine oxidase</span> Class of enzymes

Xanthine oxidase is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. These enzymes play an important role in the catabolism of purines in some species, including humans.

<span class="mw-page-title-main">Xanthinuria</span> Medical condition

Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the enzyme xanthine oxidase.

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<span class="mw-page-title-main">Dihydrolipoamide dehydrogenase</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Long-chain-aldehyde dehydrogenase</span> Protein-coding gene in the species Homo sapiens

Fatty aldehyde dehydrogenase is an aldehyde dehydrogenase enzyme that in human is encoded in the ALDH3A2 gene on chromosome 17. Aldehyde dehydrogenase enzymes function to remove toxic aldehydes that are generated by the metabolism of alcohol and by lipid peroxidation.

<span class="mw-page-title-main">UDP-glucose 6-dehydrogenase</span> Mammalian protein found in humans

UDP-glucose 6-dehydrogenase is a cytosolic enzyme that in humans is encoded by the UGDH gene.

<span class="mw-page-title-main">Dihydropyrimidine dehydrogenase (NADP+)</span> Class of enzymes

In enzymology, a dihydropyrimidine dehydrogenase (NADP+) (EC 1.3.1.2) is an enzyme that catalyzes the chemical reaction

In enzymology, an aldehyde dehydrogenase (FAD-independent) (EC 1.2.99.7) is an enzyme that catalyzes the chemical reaction

In enzymology, a phenylalanine dehydrogenase (EC 1.4.1.20) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">AKR1C1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">HSD17B4</span> Protein-coding gene in the species Homo sapiens

D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV is a protein that in humans is encoded by the HSD17B4 gene. It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism.

<span class="mw-page-title-main">NDUFV2</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial (NDUFV2) is an enzyme that in humans is encoded by the NDUFV2 gene. The encoded protein, NDUFV2, is a subunit of complex I of the mitochondrial respiratory chain, which is located on the inner mitochondrial membrane and involved in oxidative phosphorylation. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy.

<span class="mw-page-title-main">NDUFB9</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFB9 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">MOCOS</span> Protein-coding gene in the species Homo sapiens

Molybdenum cofactor sulfurase is an enzyme that in humans is encoded by the MOCOS gene.

<span class="mw-page-title-main">NDUFB11</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial is an enzyme that in humans is encoded by the NDUFB11 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 11 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain. NDUFB11 mutations have been associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency.

<span class="mw-page-title-main">Aldehyde oxidase 1</span> Protein-coding gene in the species Homo sapiens

Aldehyde oxidase 1 is an enzyme that in humans is encoded by the AOX1 gene.

<span class="mw-page-title-main">Short-chain acyl-CoA dehydrogenase</span>

Short-chain acyl-CoA dehydrogenase is an enzyme with systematic name short-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Caffeine dehydrogenase</span> Enzyme

Caffeine dehydrogenase, commonly referred to in scientific literature as caffeine oxidase, is an enzyme with the systematic name caffeine:ubiquinone oxidoreductase. The enzyme is most well known for its ability to directly oxidize caffeine, a type of methylxanthine, to trimethyluric acid. Caffeine dehydrogenase can be found in bacterium Pseudomonas sp. CBB1 and in several species within the genera Alcaligenes, Rhodococcus, and Klebsiella.

<span class="mw-page-title-main">NDUFA4</span> Protein-coding gene in the species Homo sapiens

NDUFA4, mitochondrial complex associated is a protein that in humans is encoded by the NDUFA4 gene. The NDUFA4 protein was first described to be a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. However, recent research has described NDUFA4 as a subunit of cytochrome c oxidase. Mutations in the NDUFA4 gene are associated with Leigh's syndrome.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000158125 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024066 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 "Entrez Gene: XDH xanthine dehydrogenase" . Retrieved October 25, 2012.
  6. 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.
  7. 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.
  8. 1 2 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