Alternative titles; symbols
HGNC Approved Gene Symbol: ADH4
Cytogenetic location: 4q23 Genomic coordinates (GRCh38): 4:99,123,658-99,144,297 (from NCBI)
The ADH4 gene encodes alcohol dehydrogenase 4, which belongs to class II of the ADH genes. ADH4 (pi) isozyme, characteristic of adult liver, was termed class II by Vallee and Bazzone (1983), who referred to ADH5 (chi; 103710) as class III.
Li et al. (1977) described a functionally distinct form of human liver alcohol dehydrogenase and termed it Pi-alcohol dehydrogenase. Variability from person to person was found, suggesting genetic variability. At intoxicating levels of alcohol, this enzyme may account for as much as 40% of the total ethanol oxidation rate. Unlike the other alcohol dehydrogenases, this type is not inhibited by pyrazole; hence, its name. It differs immunologically from other alcohol dehydrogenases and also has different substrate specificities; e.g., ethylene glycol is digested by other alcohol dehydrogenases but not by the Pi form.
Mardh et al. (1986) presented evidence that Pi-ADH has a physiologic role in the degradation of circulating epinephrine and norepinephrine.
McPherson et al. (1989) used a combination of somatic cell hybrid DNA analysis and in situ hybridization to localize the ADH4 gene locus to human chromosome 4q22 in the cluster of alcohol dehydrogenase genes.
Edman and Maret (1992) described RFLPs for the ADH4 and ADH5 genes. Linkage disequilibrium was detected between RFLPs in several of the 5 genes in the ADH cluster on chromosome 4. The disequilibrium between ADH4 and ADH5 indicated a hitherto unknown physical proximity of these 2 genes of different ADH classes, class II and class III, respectively.
For discussion of a possible association between variation in the ADH4 gene and alcohol dependence, see 103780.
Edman, K., Maret, W. Alcohol dehydrogenase genes: restriction fragment length polymorphisms for ADH4 (pi-ADH) and ADH5 (chi-ADH) for construction of haplotypes among different ADH classes. Hum. Genet. 90: 395-401, 1992. [PubMed: 1362387] [Full Text: https://doi.org/10.1007/BF00220466]
Li, T.-K., Bosron, W. F., Dafeldecker, W. P., Lange, L. G., Vallee, B. L. Isolation of PI-alcohol dehydrogenase of human liver: is it a determinant of alcoholism? Proc. Nat. Acad. Sci. 74: 4378-4381, 1977. [PubMed: 270680] [Full Text: https://doi.org/10.1073/pnas.74.10.4378]
Mardh, G., Dingley, A. L., Auld, D. S., Vallee, B. L. Human class II (pi) alcohol dehydrogenase has a redox-specific function in norepinephrine metabolism. Proc. Nat. Acad. Sci. 83: 8908-8912, 1986. [PubMed: 3466164] [Full Text: https://doi.org/10.1073/pnas.83.23.8908]
McPherson, J. D., Smith, M., Wagner, C., Wasmuth, J. J., Hoog, J.-O. Mapping of the class II alcohol dehydrogenase gene locus to 4q22. (Abstract) Cytogenet. Cell Genet. 51: 1043 only, 1989.
Vallee, B. L., Bazzone, T. J. Isozymes of human liver alcohol dehydrogenase. In: Rattazzi, M. C.; Scandalios, J. G.; Whitt, G. S. (eds.): Isozymes. Current Topics in Biological and Medical Research. Vol. 8. New York: Alan R. Liss 1983. Pp. 219-244.