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Gene Review

ADH5  -  alcohol dehydrogenase 5 (class III), chi...

Homo sapiens

Synonyms: ADH-3, ADHX, Alcohol dehydrogenase 5, Alcohol dehydrogenase class chi chain, Alcohol dehydrogenase class-3, ...
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Disease relevance of ADH5


Psychiatry related information on ADH5


High impact information on ADH5


Chemical compound and disease context of ADH5

  • Low FDH expression increased the formyl-THF/THF ratio nearly 10-fold, whereas THF accounted for nearly 50% of total folate in neuroblastoma with high FDH expression [4].
  • An air-stable formate dehydrogenase (FDH), an enzyme that catalyzes the oxidation of formate to carbon dioxide, was purified from the sulfate reducing organism Desulfovibrio gigas (D. gigas) NCIB 9332 [9].
  • A prospective study of the effect of alcohol consumption and ADH3 genotype on plasma steroid hormone levels and breast cancer risk [10].
  • Three different dehydrogenases able to oxidize formaldehyde were found in the Gram-positive methylotroph, Nocardia sp. 239: an NAD-dependent aldehyde dehydrogenase (NA-ADH), and NAD- and factor-dependent formaldehyde dehydrogenase (FD-FDH), and a dye-linked aldehyde dehydrogenase (DL-ADH) [11].
  • Two membrane enzymes, d-fructose dehydrogenase from Gluconobacter sp. (FDH) and sarcosine dehydrogenase from Pseudomonas putida (SDH), were for the first time immobilized onto the bilayer membranes of these type of vesicles; and the catalytic activity and enzymatic stability were measured and compared with the enzymes in a vesicle-free solution [12].

Biological context of ADH5

  • The human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC gene family consists of five known loci (ADH1-ADH5), which have been mapped close together on chromosome 4 (4q21-25) [13].
  • When its deduced amino acid sequence was compared with those of the class I, class II, and class III ADHs, the proportions of identical amino acids were 56.7%, 55.5%, and 88.7%, respectively, suggesting that the processed pseudogene was derived from an ADH5 gene [14].
  • The 5' region of ADH5 contains consensus binding sites for the transcriptional regulatory proteins, Sp1, AP2, LF-A1, NF-1, NF-A2, and NF-E1 [15].
  • ADH5 is composed of nine exons and eight introns [15].
  • A 1.5-kb upstream fragment from ADH5 was able to drive the transcription of a cat reporter gene at high levels in monkey kidney cells (CV-1) [15].

Anatomical context of ADH5

  • An electrophoretic variant for ADH-3 was observed for the enzyme in stomach, kidney, and testis extracts, and activity variation existed for this isozyme in kidney extracts [16].
  • With the glutathione-dependent formaldehyde dehydrogenase assay, we found the highest activity in the cytosol of hepatocytes and brain cells (12 and 2.6 mU/mg protein, respectively), but nuclei also exhibited significant activity (1.16 and 2.1 mU/mg protein, respectively) [17].
  • In contrast, decay of ADH3 protein was not observed throughout a 4-day period in normal keratinocytes [18].
  • In contrast, the ADH3 protein is extremely stable, and consequently is retained during the keratinocyte life span in oral mucosa [18].
  • ADH3 mRNA was expressed in basal and parabasal cell layers of oral epithelium, whereas the protein was detected throughout the cell layers [18].

Associations of ADH5 with chemical compounds


Regulatory relationships of ADH5


Other interactions of ADH5


Analytical, diagnostic and therapeutic context of ADH5

  • Here we show with PCR amplification of 3'-cDNA ends that the ADH5 gene harbors the "missing" exon [28].
  • Sequence analysis of genomic DNA confirmed that the ADH5 gene displays composite internal/terminal exons, which can be differentially processed; i.e., 3'-end generation is a result of competition between polyadenylation and splicing [28].
  • This study sought to determine whether an association exists between ADH (ADH1C previously ADH3, ADH1B*2 previously ADH2*2) genotypes, alcohol dependence, drinking history, and liver function tests in the two major ethnic groups of Trinidad and Tobago (TT) [29].
  • ADH3 mRNA and protein were further detected in homogenates of oral tissue and various oral cell cultures, including, normal, SV40T antigen-immortalized, and tumor keratinocyte lines [18].
  • The immobilization of FDH, GADH, and Cyb2 onto ODTNB-modified gold surfaces has been studied with the quartz crystal microbalance (QCM) [30].


  1. Lung cancer in humans is not associated with lifetime total alcohol consumption or with genetic variation in alcohol dehydrogenase 3 (ADH3). Freudenheim, J.L., Ram, M., Nie, J., Muti, P., Trevisan, M., Shields, P.G., Bandera, E.V., Campbell, L.A., McCann, S.E., Schunemann, H.J., Carosella, A.M., Vito, D., Russell, M., Nochajski, T.H., Goldman, R. J. Nutr. (2003) [Pubmed]
  2. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. Hines, L.M., Stampfer, M.J., Ma, J., Gaziano, J.M., Ridker, P.M., Hankinson, S.E., Sacks, F., Rimm, E.B., Hunter, D.J. N. Engl. J. Med. (2001) [Pubmed]
  3. Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers. Harty, L.C., Caporaso, N.E., Hayes, R.B., Winn, D.M., Bravo-Otero, E., Blot, W.J., Kleinman, D.V., Brown, L.M., Armenian, H.K., Fraumeni, J.F., Shields, P.G. J. Natl. Cancer Inst. (1997) [Pubmed]
  4. Regulation of folate-mediated one-carbon metabolism by 10-formyltetrahydrofolate dehydrogenase. Anguera, M.C., Field, M.S., Perry, C., Ghandour, H., Chiang, E.P., Selhub, J., Shane, B., Stover, P.J. J. Biol. Chem. (2006) [Pubmed]
  5. Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients. Muto, M., Hitomi, Y., Ohtsu, A., Ebihara, S., Yoshida, S., Esumi, H. Gut (2000) [Pubmed]
  6. The alcohol dehydrogenase system. Jörnvall, H. EXS. (1994) [Pubmed]
  7. Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials. Williams, J.T., Begleiter, H., Porjesz, B., Edenberg, H.J., Foroud, T., Reich, T., Goate, A., Van Eerdewegh, P., Almasy, L., Blangero, J. Am. J. Hum. Genet. (1999) [Pubmed]
  8. Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation. Engeland, K., Höög, J.O., Holmquist, B., Estonius, M., Jörnvall, H., Vallee, B.L. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. Purification and characterization of a tungsten-containing formate dehydrogenase from Desulfovibrio gigas. Almendra, M.J., Brondino, C.D., Gavel, O., Pereira, A.S., Tavares, P., Bursakov, S., Duarte, R., Caldeira, J., Moura, J.J., Moura, I. Biochemistry (1999) [Pubmed]
  10. A prospective study of the effect of alcohol consumption and ADH3 genotype on plasma steroid hormone levels and breast cancer risk. Hines, L.M., Hankinson, S.E., Smith-Warner, S.A., Spiegelman, D., Kelsey, K.T., Colditz, G.A., Willett, W.C., Hunter, D.J. Cancer Epidemiol. Biomarkers Prev. (2000) [Pubmed]
  11. Different types of formaldehyde-oxidizing dehydrogenases in Nocardia species 239: purification and characterization of an NAD-dependent aldehyde dehydrogenase. Van Ophem, P.W., Duine, J.A. Arch. Biochem. Biophys. (1990) [Pubmed]
  12. Enzymatic activity and stability of D-fructose dehydrogenase and sarcosine dehydrogenase immobilized onto giant vesicles. Kato, K., Walde, P., Mitsui, H., Higashi, N. Biotechnol. Bioeng. (2003) [Pubmed]
  13. A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme. Yasunami, M., Chen, C.S., Yoshida, A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  14. Cloning and sequencing of a processed pseudogene derived from a human class III alcohol dehydrogenase gene. Matsuo, Y., Yokoyama, S. Am. J. Hum. Genet. (1990) [Pubmed]
  15. Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase. Hur, M.W., Edenberg, H.J. Gene (1992) [Pubmed]
  16. Alcohol dehydrogenase isozymes in baboons: tissue distribution, catalytic properties, and variant phenotypes in liver, kidney, stomach, and testis. Holmes, R.S., Courtney, Y.R., VandeBerg, J.L. Alcohol. Clin. Exp. Res. (1986) [Pubmed]
  17. Immunocytochemical and biochemical demonstration of formaldhyde dehydrogenase (class III alcohol dehydrogenase) in the nucleus. Iborra, F.J., Renau-Piqueras, J., Portoles, M., Boleda, M.D., Guerri, C., Pares, X. J. Histochem. Cytochem. (1992) [Pubmed]
  18. Expression of alcohol dehydrogenase 3 in tissue and cultured cells from human oral mucosa. Hedberg, J.J., Höög, J.O., Nilsson, J.A., Xi, Z., Elfwing, A., Grafström, R.C. Am. J. Pathol. (2000) [Pubmed]
  19. Omega-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4. Collins, X.H., Harmon, S.D., Kaduce, T.L., Berst, K.B., Fang, X., Moore, S.A., Raju, T.V., Falck, J.R., Weintraub, N.L., Duester, G., Plapp, B.V., Spector, A.A. J. Biol. Chem. (2005) [Pubmed]
  20. Kinetic mechanism of human glutathione-dependent formaldehyde dehydrogenase. Sanghani, P.C., Stone, C.L., Ray, B.D., Pindel, E.V., Hurley, T.D., Bosron, W.F. Biochemistry (2000) [Pubmed]
  21. Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation. Sanghani, P.C., Bosron, W.F., Hurley, T.D. Biochemistry (2002) [Pubmed]
  22. Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase. Holmquist, B., Moulis, J.M., Engeland, K., Vallee, B.L. Biochemistry (1993) [Pubmed]
  23. 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. Lee, D.K., Suh, D., Edenberg, H.J., Hur, M.W. J. Biol. Chem. (2002) [Pubmed]
  24. Alcohol dehydrogenase genes: restriction fragment length polymorphisms for ADH4 (pi-ADH) and ADH5 (chi-ADH) and construction of haplotypes among different ADH classes. Edman, K., Maret, W. Hum. Genet. (1992) [Pubmed]
  25. The mammalian alcohol dehydrogenases interact in several metabolic pathways. Höög, J.O., Strömberg, P., Hedberg, J.J., Griffiths, W.J. Chem. Biol. Interact. (2003) [Pubmed]
  26. A mapping study of 13 genes on human chromosome bands 4q11-->q25. Chen, C.S., Bejcek, B.E., Kersey, J.H. Cytogenet. Cell Genet. (1995) [Pubmed]
  27. The metabolic role of human ADH3 functioning as ethanol dehydrogenase. Lee, S.L., Wang, M.F., Lee, A.I., Yin, S.J. FEBS Lett. (2003) [Pubmed]
  28. Human class V alcohol dehydrogenase (ADH5): A complex transcription unit generates C-terminal multiplicity. Strömberg, P., Höög, J.O. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  29. ADH1C*2 allele is associated with alcohol dependence and elevated liver enzymes in Trinidad and Tobago. Montane-Jaime, K., Moore, S., Shafe, S., Joseph, R., Crooks, H., Carr, L., Ehlers, C.L. Alcohol (2006) [Pubmed]
  30. Biosensors based on membrane-bound enzymes immobilized in a 5-(octyldithio)-2-nitrobenzoic acid layer on gold electrodes. Darder, M., Casero, E., Pariente, F., Lorenzo, E. Anal. Chem. (2000) [Pubmed]
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