Ma. Doll et al., IDENTIFICATION OF A NOVEL ALLELE AT THE HUMAN NAT1 ACETYLTRANSFERASE LOCUS, Biochemical and biophysical research communications, 233(3), 1997, pp. 584-591
Humans possess two N-acetyltransferase isozymes (NAT1 and NAT2). We cl
oned and sequenced a novel NAT1 allele (Genbank HSU 80835) that contai
ned nucleotide substitutions at -344 (C --> T), -40 (A --> T), 445 [G
--> A(Val --> Ile)l, 459 [G --> A(silent)], 640 [T --> G(Ser --> Ala)]
, a 9 base pair deletion between nucleotides 1065 and 1090, and 1095 (
C --> A). The novel NAT1 allele which we have designated NAT117 is si
milar to NAT111 except for a G(445)A substitution (Val(149) --> Ile)
in the NAT1 coding region. The G(445)A (Val(149) --> Ile) substitution
yielded no significant changes in levels of immunoreactivity, as dete
cted by Western blot, nor in intrinsic stability of the recombinant N-
acetyltransferase protein. However, the G(445)A (Val(149)--> Ile) subs
titution yielded expression of recombinant NAT1 protein that catalyzed
the N-acetylation of aromatic amines and the O- and N,O-acetylation o
f their N-hydroxylated metabolites at rates up to 2-fold higher than w
ild-type recombinant human NAT1. (C) 1997 American Press.