Effects of phenobarbital upon triacylglycerol metabolism in the guinea pig.
The association between hepatic microsomal enzyme induction and triacylglycerol metabolism was examined in fasting male guinea pigs injected intraperitoneally with 50 mg phenobarbital x kg-1 for 7 days. Enzyme induction was established by a significant increase in hepatic aminopyrine N-demethylase activity, cytochrome P450 content, and hepatic gamma-glutamyl-transferase activity. Increased activity of gamma-glutamyltransferase was also observed in the blood serum of treated animals. The phenobarbital-treated guinea pigs manifested increased hepatic triacylglycerol content and serum triacylglycerol concentration, accompanied by enhanced ability of cell-free fractions of liver to synthesize glycerolipids in vitro from sn-[14C]glycerol 3-phosphate and fatty acids. Microsomal phosphatidate phosphohydrolase accounted for 97% of the total liver activity of this enzyme, and its specific activity was 50-fold higher than that of the cytosolic enzyme when each was measured under optimal conditions. Activity of the cytosolic phosphohydrolase per liver doubled and that of the microsomal phosphohydrolase increased by 40% in the phenobarbital-treated guinea pigs. The microsomal, but not the cytosolic enzyme, showed a significant correlation with hepatic triacylglycerol content. Significant correlation was observed between the various parameters of hepatic microsomal enzyme induction and hepatic triacylglycerol content, suggesting that enzyme induction may promote triacylglycerol synthesis and consequent hypertriglyceridaemia in the guinea pig.
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology*; D010711:Phosphatidate Phosphatase / Q000096:biosynthesis; D014280:Triglycerides / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D014280:Triglycerides; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D005723:gamma-Glutamyltransferase; D010711:Phosphatidate Phosphatase; D010634:Phenobarbital