Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1984 Sep 1;222(2):487–493. doi: 10.1042/bj2220487

Can phosphorylation of phosphatidate phosphohydrolase by a cyclic AMP-dependent mechanism regulate its activity and subcellular distribution and control hepatic glycerolipid synthesis?

S C Butterwith, A Martin, D N Brindley
PMCID: PMC1144203  PMID: 6089770

Abstract

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.

Full text

PDF
489

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beg Z. H., Allmann D. W., Gibson D. M. Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol. Biochem Biophys Res Commun. 1973 Oct 15;54(4):1362–1369. doi: 10.1016/0006-291x(73)91137-6. [DOI] [PubMed] [Google Scholar]
  2. Berglund L., Björkhem I., Einarsson K. Apparent phosphorylation - dephosphorylation of soluble phosphatidic acid phosphatase in rat liver. Biochem Biophys Res Commun. 1982 Mar 15;105(1):288–295. doi: 10.1016/s0006-291x(82)80043-0. [DOI] [PubMed] [Google Scholar]
  3. Bowley M., Cooling J., Burditt S. L., Brindley D. N. The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase. Biochem J. 1977 Sep 1;165(3):447–454. doi: 10.1042/bj1650447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brostrom M. A., Reimann E. M., Walsh D. A., Krebs E. G. A cyclic 3',5'-amp-stimulated protein kinase from cardiac muscle. Adv Enzyme Regul. 1970;8:191–203. doi: 10.1016/0065-2571(70)90017-8. [DOI] [PubMed] [Google Scholar]
  5. Butterwith S. C., Hopewell R., Brindley D. N. Partial purification and characterization of the soluble phosphatidate phosphohydrolase of rat liver. Biochem J. 1984 Jun 15;220(3):825–833. doi: 10.1042/bj2200825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carlson C. A., Kim K. H. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem. 1973 Jan 10;248(1):378–380. [PubMed] [Google Scholar]
  7. Cascales C., Mangiapane E. H., Brindley D. N. Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to particulate fractions of isolated rat hepatocytes. Biochem J. 1984 May 1;219(3):911–916. doi: 10.1042/bj2190911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gibson D. M., Ingebritsen T. S. Reversible modulation of liver hydroxymethylglutaryl CoA reductase. Life Sci. 1978 Dec 31;23(27-28):2649–2664. doi: 10.1016/0024-3205(78)90644-6. [DOI] [PubMed] [Google Scholar]
  9. Jennings R. J., Lawson N., Fears R., Brindley D. N. Stimulation of the activities of phosphatidate phosphohydrolase and tyrosine aminotransferase in rat hepatocytes by glucocorticoids. FEBS Lett. 1981 Oct 12;133(1):119–122. doi: 10.1016/0014-5793(81)80485-1. [DOI] [PubMed] [Google Scholar]
  10. Lamb R. G., McCue S. B. The effect of fatty acid exposure on the biosynthesis of glycerolipids by cultured hepatocytes. Biochim Biophys Acta. 1983 Oct 11;753(3):356–363. doi: 10.1016/0005-2760(83)90059-0. [DOI] [PubMed] [Google Scholar]
  11. Lawson N., Jennings R. J., Fears R., Brindley D. N. Antagonistic effects of insulin on the corticosterone-induced increase of phosphatidate phosphohydrolase activity in isolated rat hepatocytes. FEBS Lett. 1982 Jun 21;143(1):9–12. doi: 10.1016/0014-5793(82)80261-5. [DOI] [PubMed] [Google Scholar]
  12. Lawson N., Pollard A. D., Jennings R. J., Brindley D. N. Effects of corticosterone and insulin on enzymes of triacylglycerol synthesis in isolated rat hepatocytes. FEBS Lett. 1982 Sep 6;146(1):204–208. doi: 10.1016/0014-5793(82)80736-9. [DOI] [PubMed] [Google Scholar]
  13. Lehtonen M. A., Savolainen M. J., Hassinen I. E. Hormonal regulation of hepatic soluble phosphatidate phosphohydrolase. Induction by cortisol in vivo and in isolated perfused rat liver. FEBS Lett. 1979 Mar 1;99(1):162–166. doi: 10.1016/0014-5793(79)80270-7. [DOI] [PubMed] [Google Scholar]
  14. Mackall J., Meredith M., Lane M. D. A mild procedure for the rapid release of cytoplasmic enzymes from cultured animal cells. Anal Biochem. 1979 May;95(1):270–274. doi: 10.1016/0003-2697(79)90216-1. [DOI] [PubMed] [Google Scholar]
  15. Miller J. P., Beck A. H., Simon L. N., Meyer R. B., Jr Induction of hepatic tyrosine aminotransferase in vivo by derivatives of cyclic adenosine 3':5'-monophosphate. J Biol Chem. 1975 Jan 25;250(2):426–431. [PubMed] [Google Scholar]
  16. Pelech S. L., Pritchard P. H., Brindley D. N., Vance D. E. Fatty acids promote translocation of CTP:phosphocholine cytidylyltransferase to the endoplasmic reticulum and stimulate rat hepatic phosphatidylcholine synthesis. J Biol Chem. 1983 Jun 10;258(11):6782–6788. [PubMed] [Google Scholar]
  17. Pelech S. L., Pritchard P. H., Brindley D. N., Vance D. E. Fatty acids reverse the cyclic AMP inhibition of triacylglycerol and phosphatidylcholine synthesis in rat hepatocytes. Biochem J. 1983 Oct 15;216(1):129–136. doi: 10.1042/bj2160129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pelech S. L., Pritchard P. H., Vance D. E. cAMP analogues inhibit phosphatidylcholine biosynthesis in cultured rat hepatocytes. J Biol Chem. 1981 Aug 25;256(16):8283–8286. [PubMed] [Google Scholar]
  19. Pollard A. D., Brindley D. N. Effects of vasopressin and corticosterone on fatty acid metabolism and on the activities of glycerol phosphate acyltransferase and phosphatidate phosphohydrolase in rat hepatocytes. Biochem J. 1984 Jan 15;217(2):461–469. doi: 10.1042/bj2170461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reimann E. M., Walsh D. A., Krebs E. G. Purification and properties of rabbit skeletal muscle adenosine 3',5'-monophosphate-dependent protein kinases. J Biol Chem. 1971 Apr 10;246(7):1986–1995. [PubMed] [Google Scholar]
  21. Rider M. H., Saggerson E. D. Regulation by noradrenaline of the mitochondrial and microsomal forms of glycerol phosphate acyltransferase in rat adipocytes. Biochem J. 1983 Jul 15;214(1):235–246. doi: 10.1042/bj2140235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Saggerson E. D., Greenbaum A. L. The effect of dietary and hormonal conditions on the activities of glycolytic enzymes in rat epididymal adipose tissue. Biochem J. 1969 Nov;115(3):405–417. doi: 10.1042/bj1150405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Soler-Argilaga C., Russell R. L., Heimberg M. Enzymatic aspects of the reduction of microsomal glycerolipid biosynthesis after perfusion of the liver with dibutyryl adenosine-3',5'-monophosphate. Arch Biochem Biophys. 1978 Oct;190(2):367–372. doi: 10.1016/0003-9861(78)90289-8. [DOI] [PubMed] [Google Scholar]
  24. Sturton R. G., Brindley D. N. Factors controlling the metabolism of phosphatidate by phosphohydrolase and phospholipase A-type activities. Effects of magnesium, calcium and amphiphilic cationic drugs. Biochim Biophys Acta. 1980 Sep 8;619(3):494–505. doi: 10.1016/0005-2760(80)90101-0. [DOI] [PubMed] [Google Scholar]
  25. Sturton R. G., Butterwith S. C., Burditt S. L., Brindley D. N. Effects of starvation, corticotropin injection and ethanol feeding on the activity and amount of phosphatidate phosphohydrolase in rat liver. FEBS Lett. 1981 Apr 20;126(2):297–300. doi: 10.1016/0014-5793(81)80265-7. [DOI] [PubMed] [Google Scholar]
  26. Walsh D. A., Perkins J. P., Brosom C. O., Ho E. S., Kreb E. G. Catlysis of the phosphrylaseinase actition reaction. J Biol Chem. 1971 Apr 10;246(7):1968–1976. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES