Alcohol dehydrogenase isozymes in adult human stomach and liver: evidence for activity of the ADH 3 locus

Ann. Hum. Genet., Lond. (1972), 35, 243 Pyinted in Great Britain Alcohol dehydrogenase isozymes in adult human stomach and liver : evidence for activity of the ADH3 locus BY MOYRA SMITH, D. A. HOPKINSON AND HARRY HARRIS M.R.C. Human Biochemical Genetics Unit, Galton Laboratory, University College London I n a previous paper (Smith, Hopkinson & Harris, 1971) we put forward a genetical hypothesis to explain the isozyme patterns of human alcohol dehydrogenase in various tissues and at different times in development. It was suggested that there are three loci each coding for a structurally distinct type of polypeptide chain; that the isozymes are dimers; and that any particular isozyme may be made up of two identical subunits coded by a specific allele at one of the loci, or of two non-identical subunits coded by alleles at two separate loci, or of two non-identical subunits coded by different alleles at the same locus. The loci were called ADH,, ADH, and ADH, and the corresponding polypeptide subunits a, /3 and y . At each of the ADH, and ADH, loci the evidence indicated that two different common alleles occur, coding for structurally distinct forms of the corresponding polypeptide. According to the hypothesis, the isozymes in the cells of a particular tissue at a given time in development depend on the relative activities of the three loci. Thus in liver, a polypeptides determined by ADH, appear to predominate in early foetal life, but in the course of foetal develop- ment /3 polypeptides determined by ADH, appear in increasing amounts, so that while in the early foetus the main isozyme observed is aa, as development proceeds the isozymes a/3 and /3/3 appear in increasing quantities. I n adult liver ADH, activity exceeds ADH, activity. In lung, kidney and the gastro-intestinal tract the total alcohol dehydrogenase activity is very much less than in liver, and the contributions made by the different loci to the total activity show striking differences. I n lung, polypeptides determined by ADH, appear to predominate both in foetal life and in the adult. I n kidney y polypeptides determined by ADH, predominate throughout foetal life but diminish after birth, and in the adult the ADH activity that can be detected appears to be mainly derived from ADH,. I n the gastro-intestinal tract y polypeptides determined by ADH, are found as in the kidney to predominate throughout foetal life. But because of lack of suitable material the situation in adult gastro-intestinal tract was not established in our earlier work. The findings reported in the present paper are concerned with two aspects of the problem. The first concerns the ADH isozymes in the adult gastro-intestinal tract. I n our previous studies we had attempted to examine this question using material from the intestine obtained at autopsy. However, sufficiently clear and consistent isozyme patterns were not obtained. We have now found, however, that adult stomach samples from autopsy give clearly defined isozyme patterns and these correspond to those previously observed in foetal kidney and foetal intestine. Thus it appears that most of the ADH activity in adult stomach is derived from the ADH, locus. The second topic we consider here concerns certain isozymes which had previously been observed in adult liver, but which at that time could not be easily accounted for in terms of the three-locus hypothesis. These isozymes occur in addition to the aa, a/3 and /3/3 isozymes of liver, and it had been noted that they show marked variations from individual to individual in their