Polychlorinated biphenyls: in vivo and in vitro modifications of phospholipid and glyceride biosynthesis

Abstract

In vivo administration of Aroclor 1254 (PCB) alters the biosynthesis of glycerides and phospholipids. Different percentages of total radioactivity distribution patterns were observed in microsome, mitochondria, and homogenate preparations from rat liver. (14C)palmitate and (U-14C)sn-glycerol-3-phosphate were differently incorporated when assayed in the same preparation, suggesting compartmentation of the substrates. Acyl CoA sn-glycerol-3-phosphate acyl transferase was inhibited by PCB in vitro. Inhibition was noncompetitive. After 30 days of dietary pretreatment with PCB, acyl CoA sn-glycerol-3-phosphate acyl transferase activity was increased in the liver. In vitro, the total radioactivity incorporated into phospholipids and glycerides was decreased in the presence of PCB. There was, however, no significant change in the percent of total distribution of radioactivity when either (U-14C)sn-glycerol-3-phosphate or (1-14C)palmitate was the substrate. PCB had no significant effect on glycerol kinase activity. PCB initially did not inhibit phosphatidate, but after prolonged incubation there was a small increase or decrease under in vitro and in vivo conditions respectively. Phosphorylase b, but not phosphorylase a, was inhibited by PCB. 2,4,5,2'4',5'-hexachlorobiphenyl inhibited sn-glycerol-3-phosphate acyl transferase, phospholipid biosynthesis, and glyceride biosynthesis. The results indicate that PCB alters biosynthesis of phospholipids and glycerides in vitro and in vivo. Apparent differences between the results obtained under the two conditions are probably due to qualitative and/or quantitative variations in metabolic products formed from PCB in vivo.