Placental arylamine N-acetyltransferase type 1: potential contributory source of urinary folate catabolite p-acetamidobenzoylglutamate during pregnancy

Human arylamine N-acetyltransferase type 1 (NAT1), better known as a drug-m etabolising enzyme, has been proposed to acetylate the folate catabolite p- aminobenzoylglutamate (p-abaglu) to N-acetamidobenzoylglutamate (ap-abaglu) which is a major urinary folate catabolite. Using mass spectroscopic analy sis, we demonstrate the formation of ap-abaglu by recombinant human NAT1 an d human placental homogenates. Using density gradient centrifugation the pl acental enzymic activity which acetylates p-aba and the placental enzymic a ctivity acetylating p-abaglu both have an S-20,S-w value of 3.25 S. This is the expected value for a monomer of human NAT1 (33 kDa). The specific NAT1 inhibitor 5-iodosalicylate inhibits acetylation of both p-aba and p-abaglu catalysed by either recombinant human NAT1 or placental samples as the sou rce of enzyme. These data demonstrate that NAT1 is the major placental enzy me involved in acetylating p-abaglu. (C) 2000 Elsevier Science B.V. All rig hts reserved.