Mammalian alcohol dehydrogenase of higher classes: analyses of human ADH5 and rat ADH6

Alcohol dehydrogenases (ADH) of classes V and VI, ADH5 and ADH6, have been defined in man and rodents, respectively. Sequence data have been obtained at cDNA and genomic levels, but limited data are available for functionalit y and substrate repertoire. The low positional identity (65%) between the t wo ADHs, place them into separate classes. We have shown that the ADH5 gene yields two differently processed mRNAs and harbors a gene organization ide ntical to other mammalian ADHs. This is probably due to an alternative spli cing in the eighth intron that results in a shorter message missing the nin th exon or a normal message with the expected number of codons. The isolate d rat ADH6 cDNA was found to be fused to ADH2 at the 5'-end. The resulting main open reading frame translates into an N-terminally extended polypeptid e. In vitro translation results in a polypeptide of about 42 kDa and furthe r, protein was possible to express in COS cells as a fusion product with Gr een Fluorescent Protein. Both ADH5 and ADH6 show genes and gene products th at are processed comparably to other mammalian ADHs and the deduced amino a cid sequences indicate a lack of ethanol dehydrogenase activity that probab ly explains why no corresponding proteins have been isolated. The functiona lity of these ADHs is therefore still an enigma. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.