UBC Theses and Dissertations
Phosphatidylcholine biosynthesis in hypercholesterolemic rats Lim, Princeton H.
The regulation of the rate of phosphatidylcholine biosynthesis was investigated in the present study. Rats fed a high cholesterol/cholate diet had elevated levels of plasma cholesterol and phospholipids and this suggested that the rate of phosphatidylcholine biosynthesis might be altered during hypercholesterolemia. The activities of the enzymes of phosphatidylcholine biosynthesis were measured and the activities of phosphocholine cytidylyltransferase in cytosol and microsomes were increased 2- to 3-fold in the livers from hypercholesterolemia rats when compared to controls. The activities of choline kinase, phosphocholine-transferase and phosphatidylethanolamine methyltransferases, however, were unchanged. The stimulation of the cytidylyltransferase was not due to an adaptive increase in the quantity of enzyme and results suggested that a phospholipid modulator was responsible for the activation of the enzyme. The rate of phosphatidylcholine biosynthesis in the liver was measured after intraportal injection of labelled choline. The estimated rate of synthesis was 2- to 3-fold higher in the hypercholesterolemia rats and this correlated with the 2- to 3-fold stimulation of phosphocholine cytidylyltransferase activity. The results clearly showed that the cytidylyltransferase activity in the liver was rate-limiting in the de novo synthesis of phosphatidylcholine during hypercholesterolemia and strongly indicated that the increase in plasma phospholipids during hypercholesterolemia was, at least in part, the result of increased synthesis of phosphatidylcholine in the liver.
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