Heavy metal inhibition of carnitine acetyltransferase activity in human placental syncytiotrophoblast: possible site of action of HgCl2, CH3HgCl, and CdCl2.
The effect of the heavy metal toxicants HgCl2, CH3HgCl, and CdCl2 on the acetylating activity of membranous carnitine acetyltransferase (CarAc) in membrane vesicles from the maternal surface of human placental syncytiotrophoblast has been investigated. CarAc was inhibited by inorganic and organic mercury and cadmium. Carnitine acetylation was inhibited by as little as 5 microM mercury, with complete inhibition at 50 microM inorganic and organic mercury. Inhibition by cadmium was incomplete (less than 60%) at 500 microM CdCl2. Kinetic studies using Hanes plots revealed a mixed type of inhibition of CarAc by the metals. Cysteine preincubation decreased the amount of inhibition of CarAc by the metals. These results indicate that the inhibition of CarAc by heavy metals occurs by binding of the sulfhydryl on the enzyme by the metals. This interaction may be a mechanism of the heavy metal-induced fetotoxicity.
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019256:Cadmium Chloride; D002332:Carnitine O-Acetyltransferase / Q000037:antagonists & inhibitors*; D003545:Cysteine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008627:Mercuric Chloride / Q000494:pharmacology; D008628:Mercury / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000494:pharmacology; D014327:Trophoblasts / Q000201:enzymology*
D008767:Methylmercury Compounds; D002104:Cadmium; D008627:Mercuric Chloride; D000123:Acetyltransferases; D002332:Carnitine O-Acetyltransferase; D008628:Mercury; D019256:Cadmium Chloride; D003545:Cysteine; C004925:methylmercuric chloride