Kinetic analyses of liver phosphatidylcholine and phosphatidylethanolamine biosynthesis using (13)C NMR spectroscopy.

Choline and ethanolamine are substrates for de novo synthesis of phosphatidylcholine (PtdC) and phosphatidylethanolamine (PtdE) through the CDP-choline and CDP-ethanolamine pathways. In liver, PtdE can also be converted to PtdC by PtdE N-methyltransferase (PEMT). We investigated these kinetics in rat liver during a 60 min infusion with (13)C-labeled choline and ethanolamine.

NMR spectroscopic analyses of liver phosphatidylcholine and phosphatidylethanolamine biosynthesis in rats exposed to peroxisome proliferators-A class of nongenotoxic hepatocarcinogens.

Peroxisome proliferators (PPs) are commercial/industrial chemicals that display tumor promoter activity in rodents. The mechanism is not completely understood, and our ability to predict tumorigenicity a priori is even less developed. Wy-14,643, perfluorooctanoic acid (PFOA), and di(2-ethylhexyl)phthalate (DEHP) are strong, moderate, and weak tumor promoters, respectively, while perfluorodecanoic acid (PFDA) lacks promoter activity.

Dose-response hapatotoxicity of the peroxisome proliferator, perfluorodecanoic acid and the relationship to phospholipid metabolism in rats.

Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator that causes hepatotoxicity but lacks tumor-promoting activity in rats. We previously showed that a single dose of PFDA at 50 mg/kg (approximately LD50) causes an elevation in liver phosphocholine (PCho) and other effects related to phospholipid metabolism. In this study, we examined metabolic effects in the dose range 2-50 mg/kg in rats.

Effects of peroxisome proliferators on rat liver phospholipids: sphingomyelin degradation may be involved in hepatotoxic mechanism of perfluorodecanoic acid.

Perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), clofibrate, di(2-ethylhexyl)phthalate (DEHP), and Wy-14,643 represent a class of compounds known as peroxisome proliferators (PPs). Such compounds induce biogenesis of liver peroxisomes and cause a varying degree of hepatotoxicity and carcinogenesis in rodents. We examined the effects of these PPs on rat hepatic lipids and phospholipid profiles using phosphorus-31 NMR spectroscopy.

Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP:phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver.

Perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) are peroxisome proliferators that cause hepatotoxicity in rodents. This study shows that PFDA activates liver phospholipase C (PLC) and inhibits CTP:phosphocholine cytidylyltransferase (CT). PLC cytosolic and microsomal activities were increased 1.