Acetylation of p-aminobenzoylglutamate, a folic acid catabolite, by recombinant human arylamine N-acetyltransferase and U937 cells.
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.
Minchin
R F
RF
Department of Pharmacology, University of Western Australia, Nedlands.
D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005971:Glutamates; D007527:Isoenzymes; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D005492:Folic Acid; C011398:4-aminobenzoylglutamic acid; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human