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Journal of Lipid Research, Vol. 12, 1-8, January 1971
Copyright © 1971 by Lipid Research, Inc.

Phenobarbital-induced alterations in phosphatidylcholine and triglyceride synthesis in hepatic endoplasmic reticulum

David L. Young , Geraldine Powell , and William O. McMillan

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27706

Biosynthetic pathways of phosphatidylcholine and triglyceride were studied in proliferating hepatic endoplasmic reticulum of rats pretreated with phenobarbital. Phosphatidylcholine accounted for the major increment in membrane phospholipid.

In vitro measurements of hepatic microsomal enzymes which catalyze phosphatidylcholine biosynthesis revealed a significant increase in specific activity of the enzyme governing phosphatidylcholine synthesis by sequential methylation of phosphatidylethanolamine. The specific activity of phosphorylcholine-glyceride transferase, which catalyzes phosphatidylcholine synthesis from d-1,2-diglyceride and CDP-choline, was not altered. Specific activity of diglyceride acyltransferase, which catalyzes triglyceride biosynthesis, was increased to a degree comparable to the increase in specific activity found in the phenobarbital-induced drug-metabolizing enzyme which oxidatively demethylates aminopyrine.

In vivo incorporation of methyl-³H from l-methionine-methyl-³H into microsomal phosphatidylcholine was significantly increased, resulting in an increased methyl-³H to choline-1,2-¹⁴C incorporation ratio of more than three times that found in control animals. A comparable increase in this incorporation ratio was noted in serum phospholipids.

The in vitro enzyme studies, in agreement with in vivo incorporation data, indicate that the increase in phosphatidylcholine content of phenobarbital-induced proliferating endoplasmic reticulum is related to increased activity of the pathway of phosphatidylcholine biosynthesis involving the sequential methylation of phosphatidylethanolamine.

Supplementary key words phosphatidylcholine • S-adenosyl-l-methionine: phosphatidylethanolamine methyltransferase • phosphorylcholine-glyceride transferase • triglyceride • diglyceride-acyltransferase • choline • l-methionine • CDP-choline • palmitoyl CoA • d-1,2-diglyceride

Submitted on February 25, 1970
Accepted on September 11, 1970

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