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Studies on the hormonal regulation of hepatic phospholipid metabolism

University of British Columbia

Investigations were carried out on the role of glucagon and calcium in the regulation of hepatic phospholipid biosynthesis. It was found that glucagon inhibits de novo phosphatidylcholine biosynthesis in cultured rat hepatocytes. This inhibition was associated with an inhibition of CTP:phosphochocline cytidylyltransferase activity, which is the regulatory enzyme for phosphatidylcholine biosynthesis. Calcium was shown to inhibit the uptake of choline in hepatocytes by decreasing the Vmax of the saturatable uptake system. It also slightly inhibited the rate of phosphatidylcholine biosynthesis by the de novo pathway, but not by the N-methylation of phosphatidylethanolamine. However, these experiments were difficult to interpret due to the use of ionophore A23187 to vary cytosolic calcium concentrations. This ionophore has many other effects on hepatocytes which could indirectly alter the synthesis of phosphatidylcholine. In vitro studies were carried out to determine the effect of calmodulin on CTP:phosphocholine cytidylyltransferase activity. Although calmodulin did not effect the activity under the conditions of the assay, an impurity of some calmodulin preparations was found which inhibited the cytidylyltransferase in a calcium independent fashion. The inhibitor had some peptide like properties. The effect of calcium on the incorporation of[3- ³H] serine into phospholipids was also investigated. Calcium was found to increase the amount of label recovered in phospholipid. It was also found that,the label was rapidly transfered from phosphatidyserine to phosphatidylethanolamine. On the basis of these results, a model is presented for the relationships between calcium and phosphatidylserine metabolism.

Text

2010-03-31

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http://hdl.handle.net/2429/23228

Biochemistry and Molecular Biology

University of British Columbia

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