Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1985 Dec 1;232(2):485–491. doi: 10.1042/bj2320485

Regulation of the translocation of phosphatidate phosphohydrolase between the cytosol and the endoplasmic reticulum of rat liver. Effects of unsaturated fatty acids, spermine, nucleotides, albumin and chlorpromazine.

R Hopewell, P Martin-Sanz, A Martin, J Saxton, D N Brindley
PMCID: PMC1152906  PMID: 3004406

Abstract

The translocation of phosphatidate phosphohydrolase between the cytosol and the microsomal membranes was investigated by using a cell-free system from rat liver. Linoleate, alpha-linolenate, arachidonate and eicosapentenoate promoted the translocation to membranes with a similar potency to that of oleate. The phosphohydrolase that associated with the membranes in the presence of [14C]oleate or 1mM-spermine coincided on Percoll gradients with the peak of rotenone-insensitive NADH-cytochrome c reductase, and in the former case with a peak of 14C. Microsomal membranes were enriched with the phosphohydrolase activity by incubation with [14C]oleate or spermine and then incubated with albumin. The phosphohydrolase activity was displaced from the membranes by albumin, and this paralleled the removal of [14C]oleate from the membranes when this acid was present. Chlorpromazine also displaced phosphatidate phosphohydrolase from the membranes, but it did not displace [14C]oleate. The effects of spermine in promoting the association of the phosphohydrolase with the membranes was inhibited by ATP, GTP, CTP, AMP and phosphate. ATP at the same concentration did not antagonize the translocating effect of oleate. From these results and previous work, it was concluded that the binding of long-chain fatty acids and their CoA esters to the endoplasmic reticulum acts as a signal for more phosphatidate phosphohydrolase to associate with these membranes and thereby to enhance the synthesis of glycerolipids, especially triacylglycerol. The translocation of the phosphohydrolase probably depends on the increased negative charge on the membranes, which could also be donated by the accumulation of phosphatidate. Chlorpromazine could oppose the translocation by donating a positive charge to the membranes.

Full text

PDF
485

Selected References

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

  1. Bates E. J., Saggerson E. D. Effects of spermine and albumin on hepatic mitochondrial and microsomal glycerol phosphate acyltransferase activities. Biochem Soc Trans. 1981 Feb;9(1):57–58. doi: 10.1042/bst0090057. [DOI] [PubMed] [Google Scholar]
  2. Brindley D. N., Bowley M. Drugs affecting the synthesis of glycerides and phospholipids in rat liver. The effects of clofibrate, halofenate, fenfluramine, amphetamine, cinchocaine, chlorpromazine, demethylimipramine, mepyramine and some of their derivatives. Biochem J. 1975 Jun;148(3):461–469. doi: 10.1042/bj1480461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brindley D. N. Intracellular translocation of phosphatidate phosphohydrolase and its possible role in the control of glycerolipid synthesis. Prog Lipid Res. 1984;23(3):115–133. doi: 10.1016/0163-7827(84)90001-8. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Butterwith S. C., Martin A., Brindley D. N. Can phosphorylation of phosphatidate phosphohydrolase by a cyclic AMP-dependent mechanism regulate its activity and subcellular distribution and control hepatic glycerolipid synthesis? Biochem J. 1984 Sep 1;222(2):487–493. doi: 10.1042/bj2220487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Halban P. A., Amherdt M., Orci L., Renold A. E. Proinsulin modified by analogues of arginine and lysine is degraded rapidly in pancreatic B-cells. Biochem J. 1984 Apr 1;219(1):91–97. doi: 10.1042/bj2190091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jamdar S. C. Glycerolipid biosynthesis in rat adipose tissue. Effect of polyamines on triglyceride synthesis. Arch Biochem Biophys. 1977 Aug;182(2):723–731. doi: 10.1016/0003-9861(77)90554-9. [DOI] [PubMed] [Google Scholar]
  8. Jamdar S. C. Hepatic lipid metabolism: effect of spermine, albumin, and Z protein on microsomal lipid formation. Arch Biochem Biophys. 1979 Jun;195(1):81–94. doi: 10.1016/0003-9861(79)90329-1. [DOI] [PubMed] [Google Scholar]
  9. Jamdar S. C., Osborne L. J. Glycerolipid biosynthesis in rat adipose tissue. 11. Effects of polyamines on Mg2+-dependent phosphatidate phosphohydrolase. Biochim Biophys Acta. 1983 Jun 16;752(1):79–88. doi: 10.1016/0005-2760(83)90235-7. [DOI] [PubMed] [Google Scholar]
  10. Jamdar S. C., Osborne L. J. Glycerolipid biosynthesis in rat adipose tissue. IX. Activation of diglyceride acyltransferase by spermine. Enzyme. 1982;28(4):387–391. doi: 10.1159/000459128. [DOI] [PubMed] [Google Scholar]
  11. Martin-Sanz P., Hopewell R., Brindley D. N. Long-chain fatty acids and their acyl-CoA esters cause the translocation of phosphatidate phosphohydrolase from the cytosolic to the microsomal fraction of rat liver. FEBS Lett. 1984 Oct 1;175(2):284–288. doi: 10.1016/0014-5793(84)80752-8. [DOI] [PubMed] [Google Scholar]
  12. Martin-Sanz P., Hopewell R., Brindley D. N. Spermine promotes the translocation of phosphatidate phosphohydrolase from the cytosol to the microsomal fraction of rat liver and it enhances the effects of oleate in this respect. FEBS Lett. 1985 Jan 7;179(2):262–266. doi: 10.1016/0014-5793(85)80531-7. [DOI] [PubMed] [Google Scholar]
  13. Moller F., Hough M. R. Effect of salts on membrane binding and activity of adipocyte phosphatidate phosphohydrolase. Biochim Biophys Acta. 1982 Jun 11;711(3):521–531. doi: 10.1016/0005-2760(82)90068-6. [DOI] [PubMed] [Google Scholar]
  14. Moller F., Wong K. H., Green P. Control of fat cell phosphohydrolase by lipolytic agents. Can J Biochem. 1981 Jan;59(1):9–15. doi: 10.1139/o81-002. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Pelech S. L., Vance D. E. Regulation of phosphatidylcholine biosynthesis. Biochim Biophys Acta. 1984 Jun 25;779(2):217–251. doi: 10.1016/0304-4157(84)90010-8. [DOI] [PubMed] [Google Scholar]
  17. Pittner R. A., Fears R., Brindley D. N. Interactions of insulin, glucagon and dexamethasone in controlling the activity of glycerol phosphate acyltransferase and the activity and subcellular distribution of phosphatidate phosphohydrolase in cultured rat hepatocytes. Biochem J. 1985 Sep 1;230(2):525–534. doi: 10.1042/bj2300525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Sottocasa G. L., Kuylenstierna B., Ernster L., Bergstrand A. An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. J Cell Biol. 1967 Feb;32(2):415–438. doi: 10.1083/jcb.32.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Walton P. A., Possmayer F. The role of Mg2+-dependent phosphatidate phosphohydrolase in pulmonary glycerolipid biosynthesis. Biochim Biophys Acta. 1984 Dec 6;796(3):364–372. doi: 10.1016/0005-2760(84)90139-5. [DOI] [PubMed] [Google Scholar]
  21. Weinhold P. A., Rounsifer M. E., Williams S. E., Brubaker P. G., Feldman D. A. CTP:phosphorylcholine cytidylyltransferase in rat lung. The effect of free fatty acids on the translocation of activity between microsomes and cytosol. J Biol Chem. 1984 Aug 25;259(16):10315–10321. [PubMed] [Google Scholar]
  22. Wilson J. E. Brain hexokinase, the prototype ambiquitous enzyme. Curr Top Cell Regul. 1980;16:1–54. doi: 10.1016/b978-0-12-152816-4.50005-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES