Effect of chlorpromazine on the synthesis, hydrolysis, and transfer of microsomal cytidine liponucleotides and mitochondrial polyglycerophosphatides.
The effect of chlorpromazine on subcellular biosynthesis, hydrolysis, and transfer of lipids and liponucleotides participating in the biosynthesis of polyglycerophosphatides in guinea pig liver was studied. Chlorpromazine showed an apparent stimulation of accumulation of phosphatidic acid and CDP-diglycerides in microsomal membranes and phosphatidylglycerolphosphate in mitochondrial membranes in a concentration-dependent manner that was influenced by incubation time and the nature of fatty acids in CDP-diglycerides. Transfer of membrane-bound CDP-diglycerides from microsomal to mitochondrial membranes was established by the CDP-diglyceride-dependent biosynthesis of phosphatidylglycerolphosphate and phosphatidylglycerol and appeared to be inhibited by the addition of chlorpromazine by about 20%. Evidence was obtained for the formation of a molecular complex between phosphatidic acid and chlorpromazine; this was thought to be responsible for the protection from phosphatidate phosphohydrolase at the concentrations of chlorpromazine and Mg2+ examined.
D000818:Animals; D002308:Cardiolipins / Q000096:biosynthesis; D002746:Chlorpromazine / Q000378:metabolism / Q000494:pharmacology*; D003567:Cytidine Diphosphate Diglycerides / Q000096:biosynthesis; D003597:Cytosine Nucleotides / Q000378:metabolism*; D006168:Guinea Pigs; D006868:Hydrolysis; D050356:Lipid Metabolism; D008081:Liposomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000096:biosynthesis / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000096:biosynthesis*
D002308:Cardiolipins; D003567:Cytidine Diphosphate Diglycerides; D003597:Cytosine Nucleotides; D008081:Liposomes; D010712:Phosphatidic Acids; D010715:Phosphatidylglycerols; C034358:phosphatidylglycerophosphate; D002746:Chlorpromazine