Arylamine N-acetyltransferase activity of the human placenta.
The fetus is exposed to almost all of the substances found in the maternal circulation whether nutrients or foreign chemicals ("xenobiotics"). The main route of exposure is the placenta. The placenta is metabolically active toward xenobiotics and the nature of the compounds reaching the fetal circulation will, in part, depend on placental biotransformation reactions. Arylamine N-acetyltransferase (NAT) catalyzes the acetyl CoA-dependent N-acetylation of primary arylamine and hydrazine substrates such as sulfamethazine, isoniazid, p-aminobenzoic acid as well as arylamine carcinogens such as 2-aminofluorene and benzidine. NAT activity is multigenically determined and can be attributed to two independently expressed proteins: NAT1 and NAT2. The acetylation capacity of the human placenta has not been investigated extensively. In the current study we identified and characterized the NAT activity of human term placenta. The kinetic data show that the activity of NAT in human placenta predominantly reflects the NAT1 enzyme. The apparent affinity (19.1 +/- 0.97 microM; mean +/- S.E.M., n = 22) and maximal velocity (3.84 +/- 0.32 nmol/min/mg; mean +/- S.E.M., n = 22) of p-aminobenzoic acid N-acetylation are similar to those measured in other tissues such as liver, blood lymphocytes, neutrophils and monocytes. In addition, there is evidence of NAT2 activity in some of the placental samples assayed, although the contribution of a small amount of NAT2 activity to the overall acetylation capacity of the placenta is likely to be small.
Derewlany
L O
LO
Division of Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
Knie
B
B
Koren
G
G
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013418:Sulfamethazine / Q000378:metabolism
D013418:Sulfamethazine; D001191:Arylamine N-Acetyltransferase; D010129:4-Aminobenzoic Acid