Can phosphorylation of phosphatidate phosphohydrolase by a cyclic AMP-dependent mechanism regulate its activity and subcellular distribution and control hepatic glycerolipid synthesis?
Incubating the particle-free supernatant of rat liver with alkaline phosphatase decreased the activity of phosphatidate phosphohydrolase by 21-29%. When the particle-free supernatant was incubated with various combinations of Mg2+, ATP, cyclic AMP and cyclic AMP-dependent protein kinase this failed to alter significantly phosphatidate phosphohydrolase activity under the conditions employed. The incubation of hepatocytes in monolayer culture with 0.5 mM-8-(4-chlorophenylthio)adenosine 3',5'-monophosphate increased the total activity of phosphatidate phosphohydrolase as measured in vitro. This also decreased the proportion of the phosphohydrolase that was associated with the membrane fraction of the cells and increased that in the cytosolic fraction. Adding 1 mM-oleate to the hepatocytes promoted the translocation of phosphatidate phosphohydrolase from the cytosol to the membrane-associated compartment. Oleate overcame the effect of the cyclic AMP analogue in favouring the cytosolic distribution of the phosphohydrolase. These results are discussed in relation to the interaction of hormonal balance and substrate supply in controlling the synthesis of phosphatidylcholine and triacylglycerol in the liver in stress and in diabetes. It is proposed that the cytosolic phosphatidate phosphohydrolase activity represents a reservoir of potential activity that becomes expressed when the enzyme translocates to the membranes on which the synthesis of glycerolipids occurs.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D005260:Female; D005989:Glycerides / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology
D005989:Glycerides; D009829:Oleic Acids; D015636:Magnesium Chloride; D019301:Oleic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D000469:Alkaline Phosphatase; D010744:Phosphoric Monoester Hydrolases; D010711:Phosphatidate Phosphatase; D008274:Magnesium