An enzymatic explanation of the differential effects of oleate and gemfibrozil on cultured hepatocyte triacylglycerol and phosphatidylcholine biosynthesis and secretion.

Autor: Lamb RG; Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298-0613., Koch JC, Bush SR
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta [Biochim Biophys Acta] 1993 Jan 10; Vol. 1165 (3), pp. 299-305.
DOI: 10.1016/0005-2760(93)90140-5
Abstrakt: Incubation (1-4 h) of primary cultures of adult rat hepatocytes with gemfibrozil (0.1-1.0 mM) significantly decreased the: (1) incorporation of [1,3-14C]glycerol into cellular triacylglycerol (30%); (2) secretion of labeled (VLDL) triacylglycerol (4-fold); and (3) oleate-induced rise in triacylglycerol biosynthesis and secretion. Gemfibrozil also increased the: (1) incorporation of labeled glycerol into cellular phosphatidylcholine (2-fold); and (2) secretion of labeled (HDL) phosphatidylcholine (10-fold). The gemfibrozil-dependent increase in the flux of labeled diacylglycerol into phosphatidylcholine is rapid (15 min) and associated with a 2-fold increase in membrane-bound phosphocholine cytidylyltransferase activity. A phosphocholine cytidylyltransferase-mediated rise in cellular CDP choline content may explain the gemfibrozil-dependent rise in phosphatidylcholine biosynthesis since homogenates of monolayers incubated with CDP choline preferentially incorporate labeled diacylglycerol into phosphatidylcholine rather than triacylglycerol. Therefore, the triacylglycerol-lowering potential of gemfibrozil may be due in part to its ability to shunt liver cell diacylglycerol into phosphatidylcholine rather than triacylglycerol. These results suggest that CDP choline may be a key regulator of the diacylglycerol branchpoint, since diacylglycerol is primarily incorporated into phosphatidylcholine or triacylglycerol depending on whether CDP choline is or is not available.
Databáze: MEDLINE