Acetylation of p-aminobenzoylglutamate, a folic acid catabolite, by recombinant human arylamine N-acetyltransferase and U937 cells

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Abstract
N-acetyl-p-aminobenzoylglutamate is a major urinary metabolite of folic acid. It is formed by acetylation of p-aminobenzoylglutamate following cleavage of the C9-N10 bond of folic acid. Using recombinant human type 1 (NAT1) and type 2 (NAT2) arylamine N-acetyltransferase, we have shown that p-aminobenzoylglutamate is a specific NAT1 substrate. At an acetyl-CoA concentration of 50 microM, the Km for p-aminobenzoylglutamate (pABG) acetylation by recombinant NAT1 was 130 +/- 13 microM. For the human pro-monocytic cell-line U937, the apparent Km was slightly higher (333 +/- 17 microM). Inhibitor studies supported NAT1-dependent acetylation of pABG by U937 cell cytosols. These studies are the first to identify a potential endogenous substrate for human NAT1 and suggest that this enzyme may be important in the cellular clearance of pABG.