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

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arylamine N-Acetyltransferase / genetics*
  • Arylamine N-Acetyltransferase / isolation & purification
  • Arylamine N-Acetyltransferase / metabolism
  • Base Sequence
  • DNA / genetics
  • DNA / isolation & purification
  • Genomic Library
  • Genotype
  • Humans
  • Isoenzymes / genetics*
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism
  • Liver / enzymology*
  • Molecular Sequence Data
  • Poly A / genetics
  • Poly A / isolation & purification
  • Polymorphism, Genetic*
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • RNA, Messenger / isolation & purification
  • Restriction Mapping

Substances

  • Isoenzymes
  • RNA, Messenger
  • Poly A
  • RNA
  • DNA
  • Arylamine N-Acetyltransferase

Associated data

  • GENBANK/D10345
  • GENBANK/D10346
  • GENBANK/D10347
  • GENBANK/D10348
  • GENBANK/D10867
  • GENBANK/D10868
  • GENBANK/D10869
  • GENBANK/D10870
  • GENBANK/D10871
  • GENBANK/D10872