DEFICIENCY OF CYTOSOLIC ARYLAMINE N-ACETYLATION IN THE DOMESTIC CAT AND WILD FELIDS CAUSED BY THE PRESENCE OF A SINGLE NAT1-LIKE GENE

The purpose of this study was to determine the molecular basis for a r elative deficiency in the cat of cytosolic arylamine N-acetyltransfera se (NAT), an enzyme family that is important in the metabolism of xeno biotics and that normally consists of at least two related enzymes, NA T1 and NAT2, N-acetyltransferase in feline liver showed high affinity (mean K-m = 2.1 mu M) for p-aminobenzoic acid, an NAT1 selective subst rate in humans and rabbits, but showed a very poor affinity (mean K-m > 10 mM) for sulfamethazine, an NAT2 selective substrate in humans and rabbits. Immunoreactive N-acetyltransferase was detected in feline li ver, bladder and colon using an NAT1-specific antipeptide antibody, bu t was not detected in any tissues using an NAT2-specific antibody. Sou thern blot analysis of genomic DNA demonstrated a single band in domes tic cats using each of six restriction digests; single bands were also found on Southern blot analysis of six wild felids. The deduced amino acid sequence of the central portion of feline N-acetyltransferase, o btained by polymerase chain reaction amplification in both domestic ca ts and seven wild felids (lion, tiger, lynx, snow leopard, bobcat, Asi an leopard cat and cheetah), contained three residues, Phe(125), Arg(1 27), and Tyr(129), which determine NAT1-like substrate specificity in humans. These results support the conclusion that cytosolic arylamine N-acetylation activity is low in the cat because of the presence of a single N-acetyltransferase that has substrate specificity, immunogenic ity and sequence characteristics similar to human NAT1, and that the u nusual presence of only a single N-acetyltransferase gene appears to b e a family wide trait shared by other felids, Pharmacogenetics 8: 169- 179 (C) 1998 Lippincott-Raven Publishers.