Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver.
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.
Deguchi
T
T
Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neurosciences, Japan.
D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015698:Genomic Library; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping
D007527:Isoenzymes; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D004247:DNA; D001191:Arylamine N-Acetyltransferase