Gene Symbol: Adh5
Description: alcohol dehydrogenase 5 (class III), chi polypeptide
Alias: Adh-5, Adh3, GSNOR, alcohol dehydrogenase class-3, ADH-B2, FALDH, FDH, GSH-FDH, S-(hydroxymethyl)glutathione dehydrogenase, S-nitrosoglutathione reductase, alcohol dehydrogenase 2, alcohol dehydrogenase B2, alcohol dehydrogenase class-III, glutathione-dependent formaldehyde dehydrogenase
Species: mouse
Products:     Adh5

Top Publications

  1. Ang H, Deltour L, Hayamizu T, Zgombić Knight M, Duester G. Retinoic acid synthesis in mouse embryos during gastrulation and craniofacial development linked to class IV alcohol dehydrogenase gene expression. J Biol Chem. 1996;271:9526-34 pubmed
    ..In addition, the finding of endogenous RA and class IV ADH mRNA in the craniofacial region has implications for the mechanism of fetal alcohol syndrome. ..
  2. Molotkov A, Fan X, Duester G. Excessive vitamin A toxicity in mice genetically deficient in either alcohol dehydrogenase Adh1 or Adh3. Eur J Biochem. 2002;269:2607-12 pubmed
    ..Here, Adh1, Adh3, and Adh4 null mutant mice have been examined following acute and chronic vitamin A excess...
  3. Rout U, Armant D. Expression of genes for alcohol and aldehyde metabolizing enzymes in mouse oocytes and preimplantation embryos. Reprod Toxicol. 2002;16:253-8 pubmed
    ..The absence of enzymes to convert ethanol to acetaldehyde, coupled with oocyte expression of the acetaldehyde-degrading enzyme, Ahd-5, may be protective for the early embryo. ..
  4. Yang Z, Wang Z, Doulias P, Wei W, Ischiropoulos H, Locksley R, et al. Lymphocyte development requires S-nitrosoglutathione reductase. J Immunol. 2010;185:6664-9 pubmed publisher
    ..In this study, we show that S-nitrosoglutathione reductase (GSNOR), a protein key to the control of protein S-nitrosylation, is important for the development of lymphocytes...
  5. Lima B, LAM G, Xie L, Diesen D, Villamizar N, Nienaber J, et al. Endogenous S-nitrosothiols protect against myocardial injury. Proc Natl Acad Sci U S A. 2009;106:6297-302 pubmed publisher
    ..following left coronary artery ligation, mice with a targeted deletion of the S-nitrosoglutathione reductase gene (GSNOR(-/-)) have reduced myocardial infarct size, preserved ventricular systolic and diastolic function, and maintained ..
  6. Que L, Liu L, Yan Y, Whitehead G, Gavett S, Schwartz D, et al. Protection from experimental asthma by an endogenous bronchodilator. Science. 2005;308:1618-21 pubmed
    ..wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs)...
  7. Liu L, Yan Y, Zeng M, Zhang J, Hanes M, Ahearn G, et al. Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell. 2004;116:617-28 pubmed
    ..We generated mice with a targeted gene deletion of S-nitrosoglutathione reductase (GSNOR), and show that they exhibit substantial increases in whole-cell S-nitrosylation, tissue damage, and mortality ..
  8. Ozawa K, Tsumoto H, Wei W, Tang C, Komatsubara A, Kawafune H, et al. Proteomic analysis of the role of S-nitrosoglutathione reductase in lipopolysaccharide-challenged mice. Proteomics. 2012;12:2024-35 pubmed publisher
    S-Nitrosoglutathione reductase (GSNOR) is a key regulator of protein S-nitrosylation, the covalent modification of cysteine residues by nitric oxide that can affect activities of many proteins...
  9. Giri P, Krug J, Kozak C, Moretti T, O Brien S, Seuanez H, et al. Cloning and comparative mapping of a human class III (chi) alcohol dehydrogenase cDNA. Biochem Biophys Res Commun. 1989;164:453-60 pubmed
    A cDNA encoding human class III (chi ADH5) alcohol dehydrogenase was isolated, sequenced and used to comparatively map this unusual ADH...

More Information


  1. Rizza S, Montagna C, Cardaci S, Maiani E, Di Giacomo G, Sánchez Quiles V, et al. S-nitrosylation of the Mitochondrial Chaperone TRAP1 Sensitizes Hepatocellular Carcinoma Cells to Inhibitors of Succinate Dehydrogenase. Cancer Res. 2016;76:4170-82 pubmed publisher
    S-nitrosoglutathione reductase (GSNOR) represents the best-documented denitrosylase implicated in regulating the levels of proteins posttranslationally modified by nitric oxide on cysteine residues by S-nitrosylation...
  2. Hatzistergos K, Paulino E, Dulce R, Takeuchi L, Bellio M, Kulandavelu S, et al. S-Nitrosoglutathione Reductase Deficiency Enhances the Proliferative Expansion of Adult Heart Progenitors and Myocytes Post Myocardial Infarction. J Am Heart Assoc. 2015;4: pubmed publisher
    ..Mice deficient in S-nitrosoglutathione reductase (GSNOR(-⁄-)), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI...
  3. Zgombić Knight M, Ang H, Foglio M, Duester G. Cloning of the mouse class IV alcohol dehydrogenase (retinol dehydrogenase) cDNA and tissue-specific expression patterns of the murine ADH gene family. J Biol Chem. 1995;270:10868-77 pubmed
    ..The results presented here indicate that the mouse has a simpler ADH gene family than the human but has conserved class IV ADH previously shown to be a very active retinol dehydrogenase in humans. ..
  4. Ozawa K, Whalen E, Nelson C, Mu Y, Hess D, Lefkowitz R, et al. S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking. Mol Cell. 2008;31:395-405 pubmed publisher
    ..Thus, beta-arrestin subserves the functional coupling of eNOS and GPCRs, and dynamic S-nitrosylation/denitrosylation of beta-arrestin 2 regulates stimulus-induced GPCR trafficking. ..
  5. Cao Y, Gomes S, Rangel E, Paulino E, Fonseca T, Li J, et al. S-nitrosoglutathione reductase-dependent PPARγ denitrosylation participates in MSC-derived adipogenesis and osteogenesis. J Clin Invest. 2015;125:1679-91 pubmed publisher
    ..Moreover, these findings provide pathophysiological and therapeutic insights regarding MSC participation in adipogenesis and osteogenesis. ..
  6. Leung J, Wei W, Liu L. S-nitrosoglutathione reductase deficiency increases mutagenesis from alkylation in mouse liver. Carcinogenesis. 2013;34:984-9 pubmed publisher
    ..S-nitrosoglutathione reductase (GSNOR), a key regulator of protein S-nitrosylation, is frequently deficient in human HCC...
  7. Brown Steinke K, Deronde K, Yemen S, Palmer L. Gender differences in S-nitrosoglutathione reductase activity in the lung. PLoS ONE. 2010;5:e14007 pubmed publisher
    ..Moreover, disruption of this eNOS-GSNO-R axis contributes to the development of PH. ..
  8. Szalai G, Duester G, Friedman R, Jia H, Lin S, Roe B, et al. Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes. Eur J Biochem. 2002;269:224-32 pubmed
    ..The mouse genes are all in the same transcriptional orientation in the order Adh4-Adh1-Adh5a-Adh5b-Adh5ps-Adh2-Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication ..
  9. Wu K, Ren R, Su W, Wen B, Zhang Y, Yi F, et al. A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation. J Biol Chem. 2014;289:20193-9 pubmed publisher
    Alcohol dehydrogenase 5 (ADH5) is a conserved enzyme for alcohol and aldehyde metabolism in mammals. Despite dynamic expression throughout neurogenesis, its role in neuronal development remains unknown...
  10. Foster M, Liu L, Zeng M, Hess D, Stamler J. A genetic analysis of nitrosative stress. Biochemistry. 2009;48:792-9 pubmed publisher
  11. Montagna C, Di Giacomo G, Rizza S, Cardaci S, Ferraro E, Grumati P, et al. S-nitrosoglutathione reductase deficiency-induced S-nitrosylation results in neuromuscular dysfunction. Antioxid Redox Signal. 2014;21:570-87 pubmed publisher
    ..aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs...
  12. Hur M, Ho W, Brown C, Goldman D, Edenberg H. Molecular cloning of mouse alcohol dehydrogenase-B2 cDNA: nucleotide sequences of the class III ADH genes evolve slowly even for silent substitutions. DNA Seq. 1992;3:167-75 pubmed
    ..Our analysis of the nucleotide sequences demonstrates that this cannot be the entire explanation, since the rate of silent (synonymous) nucleotide substitutions is also lower in the class III ADHs than in the class I ADHs. ..
  13. Pontel L, Rosado I, Burgos Barragan G, Garaycoechea J, Yu R, Arends M, et al. Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen. Mol Cell. 2015;60:177-88 pubmed publisher
    ..Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5(-/-) mice therefore accumulate formaldehyde adducts in DNA...
  14. Gonzalez Duarte R, Albalat R. Merging protein, gene and genomic data: the evolution of the MDR-ADH family. Heredity (Edinb). 2005;95:184-97 pubmed
    ..The data now available provide a comprehensive scenario, from which a reliable picture of the evolutionary history of this family can be made. ..
  15. Ang H, Deltour L, Zgombić Knight M, Wagner M, Duester G. Expression patterns of class I and class IV alcohol dehydrogenase genes in developing epithelia suggest a role for alcohol dehydrogenase in local retinoic acid synthesis. Alcohol Clin Exp Res. 1996;20:1050-64 pubmed
  16. Moon Y, Cao Y, Zhu J, Xu Y, Balkan W, Buys E, et al. GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity. Antioxid Redox Signal. 2017;26:165-181 pubmed publisher
    ..though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered...
  17. Palmer L, May W, Deronde K, Brown Steinke K, Bates J, Gaston B, et al. Ventilatory responses during and following exposure to a hypoxic challenge in conscious mice deficient or null in S-nitrosoglutathione reductase. Respir Physiol Neurobiol. 2013;185:571-81 pubmed publisher
    ..due to generation of GSNO, (2) roll-off is due to increased activity of the GSNO degrading enzyme, GSNO reductase (GSNOR), and (3) STF is limited by GSNOR activity...
  18. Zhang Y, Wu K, Su W, Zhang D, Wang P, Qiao X, et al. Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKII?. J Neurosci. 2017;37:9741-9758 pubmed publisher
    ..Here, we found that S-nitrosoglutathione reductase (GSNOR), the key enzyme that metabolizes intracellular nitric oxide (NO) and regulates S-nitrosation, was significantly ..
  19. Wei W, Li B, Hanes M, Kakar S, Chen X, Liu L. S-nitrosylation from GSNOR deficiency impairs DNA repair and promotes hepatocarcinogenesis. Sci Transl Med. 2010;2:19ra13 pubmed publisher
    ..We found that the abundance and activity of S-nitrosoglutathione reductase (GSNOR), a protein critical for control of protein S-nitrosylation, were significantly decreased in approximately 50% of ..
  20. Algar E, Holmes R. Mouse mitochondrial aldehyde dehydrogenase isozymes: purification and molecular properties. Int J Biochem. 1985;17:51-60 pubmed
    ..1 microM for the AHD-1 and AHD-5 isozyme respectively. Based upon the kinetic characteristics, it is suggested that AHD-5 may be the primary enzyme for oxidizing mitochondrial acetaldehyde during ethanol oxidation in vivo. ..
  21. Foglio M, Duester G. Characterization of the functional gene encoding mouse class III alcohol dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) and an unexpressed processed pseudogene with an intact open reading frame. Eur J Biochem. 1996;237:496-504 pubmed
    ..Reporter gene expression following transfection into mouse F9 embryonal carcinoma cells indicated that only Adh-2 possesses promoter activity. ..
  22. Tang C, Seeley E, Huang X, Wolters P, Liu L. Increased susceptibility to Klebsiella pneumonia and mortality in GSNOR-deficient mice. Biochem Biophys Res Commun. 2013;442:122-6 pubmed publisher
    S-nitrosoglutathione reductase (GSNOR) is a key denitrosylase and critically important for protecting immune and other cells from nitrosative stress...
  23. Goto M, Kitamura H, Alam M, Ota N, Haseba T, Akimoto T, et al. Alcohol dehydrogenase 3 contributes to the protection of liver from nonalcoholic steatohepatitis. Genes Cells. 2015;20:464-80 pubmed publisher
    ..b>ADH3 is a highly conserved bifunctional enzyme involved in formaldehyde detoxification and termination of nitric oxide ..
  24. Probert F, Rice P, Scudamore C, Wells S, Williams R, Hough T, et al. ¹H NMR metabolic profiling of plasma reveals additional phenotypes in knockout mouse models. J Proteome Res. 2015;14:2036-45 pubmed publisher
    ..In the remaining 16 lines, no ex vivo abnormal phenotypes were observed. Plasma (1)H NMR spectroscopy can therefore provide a novel perspective on the function of knocked-out genes. ..
  25. Sanghani P, Davis W, Fears S, Green S, Zhai L, Tang Y, et al. Kinetic and cellular characterization of novel inhibitors of S-nitrosoglutathione reductase. J Biol Chem. 2009;284:24354-62 pubmed publisher
    S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in the regulation of S-nitrosothiols (SNOs) in vivo...
  26. Westerlund M, Galter D, Carmine A, Olson L. Tissue- and species-specific expression patterns of class I, III, and IV Adh and Aldh 1 mRNAs in rodent embryos. Cell Tissue Res. 2005;322:227-36 pubmed
  27. Deltour L, Foglio M, Duester G. Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. J Biol Chem. 1999;274:16796-801 pubmed
    Targeting of mouse alcohol dehydrogenase genes Adh1, Adh3, and Adh4 resulted in null mutant mice that all developed and reproduced apparently normally but differed markedly in clearance of ethanol and formaldehyde plus metabolism of ..
  28. Elphinstone R, Besla R, Shikatani E, Lu Z, Hausladen A, Davies M, et al. S-Nitrosoglutathione Reductase Deficiency Confers Improved Survival and Neurological Outcome in Experimental Cerebral Malaria. Infect Immun. 2017;85: pubmed publisher
    ..we hypothesized that animals deficient in the SNO-metabolizing enzyme, S-nitrosoglutathione reductase (GSNOR), which exhibit enhanced S-nitrosylation, would have improved outcomes in a preclinical model of cerebral ..
  29. Jiang H, Polhemus D, Islam K, Torregrossa A, Li Z, Potts A, et al. Nebivolol Acts as a S-Nitrosoglutathione Reductase Inhibitor: A New Mechanism of Action. J Cardiovasc Pharmacol Ther. 2016;21:478-85 pubmed publisher
    ..One of the first described is known as S-nitrosoglutathione reductase (GSNOR)...
  30. Cox A, Saunders D, Kelsey P, Conway A, Tesmenitsky Y, Marchini J, et al. S-nitrosothiol signaling regulates liver development and improves outcome following toxic liver injury. Cell Rep. 2014;6:56-69 pubmed publisher
    ..After acetaminophen (APAP) exposure, inhibition of the enzymatic regulator S-nitrosoglutathione reductase (GSNOR) minimized toxic liver damage, increased cell proliferation, and improved survival through sustained activation of ..
  31. Palmer L, Kimberly deRonde -, Brown Steinke K, Gunter S, Jyothikumar V, Forbes M, et al. Hypoxia-induced changes in protein s-nitrosylation in female mouse brainstem. Am J Respir Cell Mol Biol. 2015;52:37-45 pubmed publisher regulated by platelet-derived growth factor receptor-? (PDGFR-?) and S-nitrosoglutathione (GSNO) reductase (GSNOR). S-nitrosylation inhibits activities of NMDAR and nNOS, but enhances GSNOR activity...
  32. Wei W, Yang Z, Tang C, Liu L. Targeted deletion of GSNOR in hepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-DNA alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine. Carcinogenesis. 2011;32:973-7 pubmed publisher
    S-nitrosoglutathione reductase (GSNOR), a ubiquitously expressed protein central to the control of protein S-nitrosylation, plays critical roles in many biological systems...
  33. Tang C, Wei W, Hanes M, Liu L. Hepatocarcinogenesis driven by GSNOR deficiency is prevented by iNOS inhibition. Cancer Res. 2013;73:2897-904 pubmed publisher
    ..nitric oxide synthase (iNOS) and with genetic deletion of the major denitrosylase S-nitrosoglutathione reductase (GSNOR/ADH5). However, their causal involvement in human HCC is not established...
  34. Straub A, Billaud M, Johnstone S, Best A, Yemen S, Dwyer S, et al. Compartmentalized connexin 43 s-nitrosylation/denitrosylation regulates heterocellular communication in the vessel wall. Arterioscler Thromb Vasc Biol. 2011;31:399-407 pubmed publisher
    ..This study provides evidence for compartmentalized S-nitrosylation/denitrosylation in the regulation of smooth muscle cell to endothelial cell communication. ..
  35. Beigi F, Gonzalez D, Minhas K, Sun Q, Foster M, Khan S, et al. Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function. Proc Natl Acad Sci U S A. 2012;109:4314-9 pubmed publisher
    ..Here, we show that S-nitrosoglutathione reductase (GSNOR), an enzyme that governs levels of S-nitrosylation by promoting protein denitrosylation, regulates both peripheral ..
  36. Sips P, Irie T, Zou L, Shinozaki S, Sakai M, Shimizu N, et al. Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression. Am J Physiol Heart Circ Physiol. 2013;304:H1134-46 pubmed publisher
    ..system via protein S-nitrosylation, which is negatively regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme promoting denitrosylation...
  37. Gomes S, Rangel E, Premer C, Dulce R, Cao Y, Florea V, et al. S-nitrosoglutathione reductase (GSNOR) enhances vasculogenesis by mesenchymal stem cells. Proc Natl Acad Sci U S A. 2013;110:2834-9 pubmed publisher
    ..of NO signaling in MSCs derived from WT mice and mice homozygous for a deletion of S-nitrosoglutathione reductase (GSNOR(-/-)), a denitrosylase that regulates S-nitrosylation...
  38. Edenberg H, Brown C, Carr L, Ho W, Hur M. Alcohol dehydrogenase gene expression and cloning of the mouse chi-like ADH. Adv Exp Med Biol. 1991;284:253-62 pubmed