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The genotype at the NAT1* locus of an interethnic population of 38 unrelated subjects was determined by direct sequencing of 1.6-kb fragments amplified by PCR. The coding exon alone and together with the 3' noncoding exon of the wild-type (NAT1*4) and the three mutant alleles (NAT1*10, *11, and *16) detected was expressed in Escherichia coli and COS-1(More)
Arylhydroxamic acid N,O-acyltransferase and Co-ASAc-dependent N-acetyltransferase activities were measured simultaneously in liver cytosols from rabbits of known acetylator phenotype. Both activities were high in rapid acetylator rabbits and low in slow acetylator rabbits indicating that these two acetyl transfer steps in the metabolic activation of certain(More)
Liver and gut mucosa N-acetyltransferase (NAT) cytosol (105,000 x g) was prepared from selected lines of New Zealand White rapid and slow acetylator rabbits bred and housed at the University of Michigan, and from inbred and partially inbred rabbits obtained from The Jackson Laboratory. Liver NAT activity was determined with p-aminobenzoic acid,(More)
The pharmacokinetics of isoniazid in man are described. Pronounced interindividual variation in circulating isoniazid concentration and clearance which occur after dosing with the drug are associated with hereditary differences in the acetylator status. The variations in rate of isoniazid inactivation and elimination in different (rapid and slow) acetylator(More)
Investigations in the rabbit have indicated the existence of more than one N-acetyltransferase (EC At least two enzymes, possibly isoenzymes, were partially characterized. The enzymes differed in their tissue distribution, substrate specificity, stability and pH characteristics. One of the enzymes was primarily associated with liver and gut and(More)
An inbred mouse model for the human N-acetylation polymorphism has been used to investigate the biochemical basis for the arylamine N-acetylation polymorphism and the relationship between the cytosolic enzymes arylamine N-acetyltransferase (NAT), arylhydroxamic acid N,O-acyltransferase, and N-hydroxyarylamine O-acetyltransferase. Biochemical studies of(More)