# ADH5

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**Alcohol dehydrogenase class-3** is an [enzyme](/source/Enzyme) that in [humans](/source/Human) is encoded by the *ADH5* [gene](/source/Gene).[1][2][3]

This gene encodes [glutathione](/source/Glutathione)-dependent [formaldehyde dehydrogenase](/source/Formaldehyde_dehydrogenase) or the class III [alcohol dehydrogenase](/source/Alcohol_dehydrogenase) chi subunit, which is a member of the [alcohol](/source/Alcohol_(chemistry)) dehydrogenase family. Members of this family [metabolize](/source/Metabolism) a wide variety of [substrates](/source/Substrate_(chemistry)), including [ethanol](/source/Ethanol), [retinol](/source/Retinol), other [aliphatic alcohols](/source/Aliphatic_compound), [hydroxysteroids](/source/Hydroxysteroids), and [lipid peroxidation](/source/Lipid_peroxidation) products. Class III alcohol dehydrogenase is a [homodimer](/source/Homodimer) composed of 2 chi subunits. It has virtually no activity for ethanol [oxidation](/source/Oxidation), but exhibits high activity for oxidation of long-chain [primary alcohols](/source/Primary_alcohol) and for oxidation of S-hydroxymethyl-glutathione, a spontaneous [adduct](/source/Adduct) between formaldehyde and glutathione.

This enzyme is an important component of [cellular metabolism](/source/Cellular_metabolism) for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes [lacrymation](/source/Lacrymation), [rhinitis](/source/Rhinitis), [pharyngitis](/source/Pharyngitis), and [contact dermatitis](/source/Contact_dermatitis).[3]

## Clinical significance

Mutations of the *ADH5* gene and *[ALDH2](/source/ALDH2)* gene cause [AMED syndrome](/source/AMED_syndrome), an autosomal recessive [digenic](/source/Digenic_disorder) multisystem disorder characterized by global developmental delay with impaired intellectual development, short stature, growth impairment and early development of [myelodysplastic syndrome](/source/Myelodysplastic_syndrome) and bone marrow failure. The syndrome was first described in 2020.[4]

## References

1. Hur MW, Edenberg HJ (Dec 1992). "Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase". *Gene*. **121** (2): 305–11. [doi:10.1016/0378-1119(92)90135-C](https://doi.org/10.1016/0378-1119(92)90135-C). [PMID 1446828](https://pubmed.ncbi.nlm.nih.gov/1446828)

1. Adinolfi A, Adinolfi M, Hopkinson DA (May 1984). "Immunological and biochemical characterization of the human alcohol dehydrogenase chi-ADH isozyme". *Ann Hum Genet*. **48** (Pt 1): 1–10. [doi:10.1111/j.1469-1809.1984.tb00828.x](https://doi.org/10.1111/j.1469-1809.1984.tb00828.x). [PMID 6424546](https://pubmed.ncbi.nlm.nih.gov/6424546). [S2CID 85113864](https://api.semanticscholar.org/CorpusID:85113864)

1. ["Entrez Gene: ADH5 alcohol dehydrogenase 5 (class III), chi polypeptide"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=128)

1. Kniffin, Cassandra L. (27 November 2023 [Originally published on 13 January 2021]). ["AMED SYNDROME, DIGENIC; AMEDS"](https://www.omim.org/entry/619151). *Online Mendelian Inheritance in Man*. Johns Hopkins University. #619151. Retrieved 1 May 2024.

## Further reading

- Iborra FJ, Renau-Piqueras J, Portoles M (1992). "Immunocytochemical and biochemical demonstration of formaldhyde dehydrogenase (class III alcohol dehydrogenase) in the nucleus.". *J. Histochem. Cytochem.*. **40** (12): 1865–78. [doi:10.1177/40.12.1453005](https://doi.org/10.1177/40.12.1453005). [PMID 1453005](https://pubmed.ncbi.nlm.nih.gov/1453005)
- Giri PR, Krug JF, Kozak C (1989). ["Cloning and comparative mapping of a human class III (chi) alcohol dehydrogenase cDNA."](https://zenodo.org/record/1253802). *Biochem. Biophys. Res. Commun.*. **164** (1): 453–60. [doi:10.1016/0006-291X(89)91741-5](https://doi.org/10.1016/0006-291X(89)91741-5). [PMID 2679557](https://pubmed.ncbi.nlm.nih.gov/2679557)
- Sharma CP, Fox EA, Holmquist B (1989). "cDNA sequence of human class III alcohol dehydrogenase.". *Biochem. Biophys. Res. Commun.*. **164** (2): 631–7. [doi:10.1016/0006-291X(89)91507-6](https://doi.org/10.1016/0006-291X(89)91507-6). [PMID 2818582](https://pubmed.ncbi.nlm.nih.gov/2818582)
- Beisswenger TB, Holmquist B, Vallee BL (1986). "chi-ADH is the sole alcohol dehydrogenase isozyme of mammalian brains: implications and inferences.". *Proc. Natl. Acad. Sci. U.S.A.*. **82** (24): 8369–73. [doi:10.1073/pnas.82.24.8369](https://doi.org/10.1073/pnas.82.24.8369). [PMC 390917](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC390917). [PMID 2934732](https://pubmed.ncbi.nlm.nih.gov/2934732)
- Dafeldecker WP, Vallee BL (1986). "Organ-specific human alcohol dehydrogenase: isolation and characterization of isozymes from testis.". *Biochem. Biophys. Res. Commun.*. **134** (3): 1056–63. [doi:10.1016/0006-291X(86)90358-X](https://doi.org/10.1016/0006-291X(86)90358-X). [PMID 2936344](https://pubmed.ncbi.nlm.nih.gov/2936344)
- Kaiser R, Holmquist B, Hempel J (1988). "Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes.". *Biochemistry*. **27** (4): 1132–40. [doi:10.1021/bi00404a009](https://doi.org/10.1021/bi00404a009). [PMID 3365377](https://pubmed.ncbi.nlm.nih.gov/3365377)
- Khokha AM, Voronov PP, Zimatkin SM (1994). "[Immunoenzyme and immunohistochemical analysis of class III alcohol dehydrogenase from human testis]". *Biokhimiia*. **59** (7): 997–1002. [PMID 7948423](https://pubmed.ncbi.nlm.nih.gov/7948423)
- Engeland K, Höög JO, Holmquist B (1993). "Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation.". *Proc. Natl. Acad. Sci. U.S.A.*. **90** (6): 2491–4. [Bibcode:1993PNAS...90.2491E](https://ui.adsabs.harvard.edu/abs/1993PNAS...90.2491E). [doi:10.1073/pnas.90.6.2491](https://doi.org/10.1073/pnas.90.6.2491). [PMC 46113](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46113). [PMID 8460164](https://pubmed.ncbi.nlm.nih.gov/8460164)
- Holmquist B, Moulis JM, Engeland K, Vallee BL (1993). "Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase.". *Biochemistry*. **32** (19): 5139–44. [doi:10.1021/bi00070a024](https://doi.org/10.1021/bi00070a024). [PMID 8494891](https://pubmed.ncbi.nlm.nih.gov/8494891)
- Engeland K, Maret W (1993). "Extrahepatic, differential expression of four classes of human alcohol dehydrogenase.". *Biochem. Biophys. Res. Commun.*. **193** (1): 47–53. [doi:10.1006/bbrc.1993.1588](https://doi.org/10.1006/bbrc.1993.1588). [PMID 8503936](https://pubmed.ncbi.nlm.nih.gov/8503936)
- Yang ZN, Bosron WF, Hurley TD (1997). "Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase.". *J. Mol. Biol.*. **265** (3): 330–43. [doi:10.1006/jmbi.1996.0731](https://doi.org/10.1006/jmbi.1996.0731). [PMID 9018047](https://pubmed.ncbi.nlm.nih.gov/9018047)
- Mori O, Haseba T, Kameyama K (2000). "Histological distribution of class III alcohol dehydrogenase in human brain.". *Brain Res.*. **852** (1): 186–90. [doi:10.1016/S0006-8993(99)02201-5](https://doi.org/10.1016/S0006-8993(99)02201-5). [PMID 10661511](https://pubmed.ncbi.nlm.nih.gov/10661511). [S2CID 23510523](https://api.semanticscholar.org/CorpusID:23510523)
- Sanghani PC, Stone CL, Ray BD (2000). "Kinetic mechanism of human glutathione-dependent formaldehyde dehydrogenase.". *Biochemistry*. **39** (35): 10720–9. [doi:10.1021/bi9929711](https://doi.org/10.1021/bi9929711). [PMID 10978156](https://pubmed.ncbi.nlm.nih.gov/10978156)
- Lee DK, Suh D, Edenberg HJ, Hur MW (2002). "POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1.". *J. Biol. Chem.*. **277** (30): 26761–8. [doi:10.1074/jbc.M202078200](https://doi.org/10.1074/jbc.M202078200). [PMID 12004059](https://pubmed.ncbi.nlm.nih.gov/12004059)
- Jelski W, Chrostek L, Szmitkowski M, Laszewicz W (2002). "Activity of class I, II, III, and IV alcohol dehydrogenase isoenzymes in human gastric mucosa.". *Dig. Dis. Sci.*. **47** (7): 1554–7. [doi:10.1023/A:1015871219922](https://doi.org/10.1023/A:1015871219922). [PMID 12141816](https://pubmed.ncbi.nlm.nih.gov/12141816). [S2CID 31197228](https://api.semanticscholar.org/CorpusID:31197228)
- Sanghani PC, Robinson H, Bosron WF, Hurley TD (2002). "Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes.". *Biochemistry*. **41** (35): 10778–86. [doi:10.1021/bi0257639](https://doi.org/10.1021/bi0257639). [PMID 12196016](https://pubmed.ncbi.nlm.nih.gov/12196016)
- Strausberg RL, Feingold EA, Grouse LH (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". *Proc. Natl. Acad. Sci. U.S.A.*. **99** (26): 16899–903. [Bibcode:2002PNAS...9916899M](https://ui.adsabs.harvard.edu/abs/2002PNAS...9916899M). [doi:10.1073/pnas.242603899](https://doi.org/10.1073/pnas.242603899). [PMC 139241](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139241). [PMID 12477932](https://pubmed.ncbi.nlm.nih.gov/12477932)
- Sanghani PC, Bosron WF, Hurley TD (2003). "Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation.". *Biochemistry*. **41** (51): 15189–94. [doi:10.1021/bi026705q](https://doi.org/10.1021/bi026705q). [PMID 12484756](https://pubmed.ncbi.nlm.nih.gov/12484756)

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Adapted from the Wikipedia article [ADH5](https://en.wikipedia.org/wiki/ADH5) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/ADH5?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.