The effects of dietary modification, starvation, stress and diabetes on the activity of phosphatidate phosphohydrolase are discussed. Evidence is presented that this enzyme is involved in controlling the rate of triacylglycerol synthesis in the liver. Drugs such as fenfluramine and benfluorex are able to inhibit phosphatidate phosphohydrolase by interacting with the substrate. This decreases the rate of triacylglycerol synthesis and redirects the route of glycerolipid metabolism. Benfluroex also partly prevents the ethanol-induced increase in triacylglycerol synthesis and in phosphohydrolase activity. The implications of these findings are discussed with respect to the mode of action of fenfluramine and benfluorex and to the control of triacylglycerol synthesis.
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