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J Biol Chem. 1992 Sep 5;267(25):18140-7.

Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver.

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  • Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neurosciences, Japan.


Fifty human livers obtained at autopsy were analyzed for N-acetyltransferase and classified into six genotypes. Determination of N-acetyltransferase activity and proteins from supernatants of liver homogenates indicate that genotype I corresponds to rapid acetylator, genotypes II and III to intermediate acetylator, and genotypes IV, V, and VI to slow acetylator phenotypes. Northern blot analysis shows that levels of mRNA for N-acetyltransferase in the livers do not markedly differ among the six genotypes. Three alleles of the N-acetyltransferase gene were cloned and sequenced. mRNA is coded in two exons. Comparison of alleles 2 and 3, which correspond to low N-acetyltransferase activity, with allele 1, which corresponds to high N-acetyltransferase activity, revealed several polymorphisms. Two gene sequence differences occur in the coding exons of alleles 2 and 3, one of which would produce different amino acids in the proteins. Those sequence differences that lead to amino acid substitutions result in a loss of BamHI and TaqI sites for alleles 2 and 3, respectively. Expression studies of the alleles in Chinese hamster ovary cells show that allele 1 expresses high levels of N-acetyltransferase activity and enzyme protein, while alleles 2 and 3 express low levels of both protein and activity.

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