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-metabolising 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 analysis, we demonstrate the formation of ap-abaglu by recombinant human NAT1 and human placental homogenates. Using density gradient centrifugation the placental enzymic activity which acetylates p-aba and the placental enzymic activity acetylating p-abaglu both have an S(20,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 source of enzyme. These data demonstrate that NAT1 is the major placental enzyme involved in acetylating p-abaglu.
Upton
A
A
Department of Pharmacology, University of Oxford, Oxford, UK.
Smelt
V
V
Mushtaq
A
A
Aplin
R
R
Johnson
N
N
Mardon
H
H
Sim
E
E
D010129:4-Aminobenzoic Acid / Q000378:metabolism* / Q000652:urine; D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005971:Glutamates; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013058:Mass Spectrometry; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy / Q000378:metabolism* / Q000652:urine; D062366:para-Aminobenzoates
D004791:Enzyme Inhibitors; D005971:Glutamates; D007527:Isoenzymes; D062366:para-Aminobenzoates; C030903:N-(4-acetamidobenzoyl)-L-glutamic acid; D005492:Folic Acid; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D010129:4-Aminobenzoic Acid