Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Apr;84(8):2170–2174. doi: 10.1073/pnas.84.8.2170

Pathway for inositol 1,3,4-trisphosphate and 1,4-bisphosphate metabolism.

R C Inhorn, V S Bansal, P W Majerus
PMCID: PMC304610  PMID: 3031669

Abstract

We prepared [3H]inositol-,3-[32P]phosphate-and 4-[32P]phosphate-labeled inositol phosphate substrates to investigate the metabolism of inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate. In crude extracts of calf brain, inositol 1,3,4-trisphosphate is first converted to inositol 3,4-bisphosphate, then the inositol 3,4-bisphosphate intermediate is further converted to inositol 3-phosphate. Similarly, inositol 1,4-bisphosphate is converted to inositol 4-phosphate, and no inositol 1-phosphate is formed. We partially purified an enzyme that we tentatively name inositol polyphosphate 1-phosphatase. This cytosolic enzyme converts inositol 1,3,4-trisphosphate to inositol 3,4-bisphosphate and also converts inositol 1,4-bisphosphate to inositol 4-phosphate. The enzyme does not utilize inositol 1,3,4,5-tetrakisphosphate, inositol 1,4,5-trisphosphate, or inositol 1-phosphate as substrates. Thus we propose a new scheme for inositol phosphate metabolism. According to this pathway inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate are degraded to inositol 4-phosphate. Inositol 1-phosphate, which is the major inositol monophosphate formed in stimulated brain, is derived either from phospholipase C cleavage of phosphatidylinositol or from the degradation of inositol cyclic phosphates.

Full text

PDF
2170

Selected References

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

  1. Auchus R. J., Kaiser S. L., Majerus P. W. Synthesis of inositol 1,2-(cyclic)-4,5-trisphosphate. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1206–1209. doi: 10.1073/pnas.84.5.1206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Batty I. R., Nahorski S. R., Irvine R. F. Rapid formation of inositol 1,3,4,5-tetrakisphosphate following muscarinic receptor stimulation of rat cerebral cortical slices. Biochem J. 1985 Nov 15;232(1):211–215. doi: 10.1042/bj2320211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  5. Burgess G. M., Godfrey P. P., McKinney J. S., Berridge M. J., Irvine R. F., Putney J. W., Jr The second messenger linking receptor activation to internal Ca release in liver. Nature. 1984 May 3;309(5963):63–66. doi: 10.1038/309063a0. [DOI] [PubMed] [Google Scholar]
  6. Burgess G. M., McKinney J. S., Irvine R. F., Putney J. W., Jr Inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate formation in Ca2+-mobilizing-hormone-activated cells. Biochem J. 1985 Nov 15;232(1):237–243. doi: 10.1042/bj2320237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connolly T. M., Bross T. E., Majerus P. W. Isolation of a phosphomonoesterase from human platelets that specifically hydrolyzes the 5-phosphate of inositol 1,4,5-trisphosphate. J Biol Chem. 1985 Jul 5;260(13):7868–7874. [PubMed] [Google Scholar]
  8. Connolly T. M., Wilson D. B., Bross T. E., Majerus P. W. Isolation and characterization of the inositol cyclic phosphate products of phosphoinositide cleavage by phospholipase C. Metabolism in cell-free extracts. J Biol Chem. 1986 Jan 5;261(1):122–126. [PubMed] [Google Scholar]
  9. Dawson R. M., Freinkel N., Jungalwala F. B., Clarke N. The enzymic formation of myoinositol 1:2-cyclic phosphate from phosphatidylinositol. Biochem J. 1971 May;122(4):605–607. doi: 10.1042/bj1220605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Downes C. P., Hawkins P. T., Irvine R. F. Inositol 1,3,4,5-tetrakisphosphate and not phosphatidylinositol 3,4-bisphosphate is the probable precursor of inositol 1,3,4-trisphosphate in agonist-stimulated parotid gland. Biochem J. 1986 Sep 1;238(2):501–506. doi: 10.1042/bj2380501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Downes C. P., Mussat M. C., Michell R. H. The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane. Biochem J. 1982 Apr 1;203(1):169–177. doi: 10.1042/bj2030169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hallcher L. M., Sherman W. R. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem. 1980 Nov 25;255(22):10896–10901. [PubMed] [Google Scholar]
  13. Hansen C. A., Mah S., Williamson J. R. Formation and metabolism of inositol 1,3,4,5-tetrakisphosphate in liver. J Biol Chem. 1986 Jun 25;261(18):8100–8103. [PubMed] [Google Scholar]
  14. Hawkins P. T., Stephens L., Downes C. P. Rapid formation of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. Biochem J. 1986 Sep 1;238(2):507–516. doi: 10.1042/bj2380507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hofmann S. L., Majerus P. W. Identification and properties of two distinct phosphatidylinositol-specific phospholipase C enzymes from sheep seminal vesicular glands. J Biol Chem. 1982 Jun 10;257(11):6461–6469. [PubMed] [Google Scholar]
  16. Irvine R. F., Letcher A. J., Heslop J. P., Berridge M. J. The inositol tris/tetrakisphosphate pathway--demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues. Nature. 1986 Apr 17;320(6063):631–634. doi: 10.1038/320631a0. [DOI] [PubMed] [Google Scholar]
  17. Irvine R. F., Letcher A. J., Lander D. J., Berridge M. J. Specificity of inositol phosphate-stimulated Ca2+ mobilization from Swiss-mouse 3T3 cells. Biochem J. 1986 Nov 15;240(1):301–304. doi: 10.1042/bj2400301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Irvine R. F., Letcher A. J., Lander D. J., Downes C. P. Inositol trisphosphates in carbachol-stimulated rat parotid glands. Biochem J. 1984 Oct 1;223(1):237–243. doi: 10.1042/bj2230237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
  20. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  21. Roach P. D., Palmer F. B. Human erythrocyte cytosol phosphatidyl-inositol-bisphosphate phosphatase. Biochim Biophys Acta. 1981 Oct 13;661(2):323–333. doi: 10.1016/0005-2744(81)90021-8. [DOI] [PubMed] [Google Scholar]
  22. Ross T. S., Majerus P. W. Isolation of D-myo-inositol 1:2-cyclic phosphate 2-inositolphosphohydrolase from human placenta. J Biol Chem. 1986 Aug 25;261(24):11119–11123. [PubMed] [Google Scholar]
  23. Sherman W. R., Munsell L. Y., Gish B. G., Honchar M. P. Effects of systemically administered lithium on phosphoinositide metabolism in rat brain, kidney, and testis. J Neurochem. 1985 Mar;44(3):798–807. doi: 10.1111/j.1471-4159.1985.tb12886.x. [DOI] [PubMed] [Google Scholar]
  24. Siess W. Evidence for the formation of inositol 4-monophosphate in stimulated human platelets. FEBS Lett. 1985 Jun 3;185(1):151–156. doi: 10.1016/0014-5793(85)80760-2. [DOI] [PubMed] [Google Scholar]
  25. Storey D. J., Shears S. B., Kirk C. J., Michell R. H. Stepwise enzymatic dephosphorylation of inositol 1,4,5-trisphosphate to inositol in liver. Nature. 1984 Nov 22;312(5992):374–376. doi: 10.1038/312374a0. [DOI] [PubMed] [Google Scholar]
  26. Takimoto K., Okada M., Matsuda Y., Nakagawa H. Purification and properties of myo-inositol-1-phosphatase from rat brain. J Biochem. 1985 Aug;98(2):363–370. doi: 10.1093/oxfordjournals.jbchem.a135290. [DOI] [PubMed] [Google Scholar]
  27. Turk J., Wolf B. A., McDaniel M. L. Glucose-induced accumulation of inositol trisphosphates in isolated pancreatic islets. Predominance of the 1,3,4-isomer. Biochem J. 1986 Jul 1;237(1):259–263. doi: 10.1042/bj2370259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilson D. B., Bross T. E., Hofmann S. L., Majerus P. W. Hydrolysis of polyphosphoinositides by purified sheep seminal vesicle phospholipase C enzymes. J Biol Chem. 1984 Oct 10;259(19):11718–11724. [PubMed] [Google Scholar]
  29. Wilson D. B., Bross T. E., Sherman W. R., Berger R. A., Majerus P. W. Inositol cyclic phosphates are produced by cleavage of phosphatidylphosphoinositols (polyphosphoinositides) with purified sheep seminal vesicle phospholipase C enzymes. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4013–4017. doi: 10.1073/pnas.82.12.4013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wilson D. B., Connolly T. M., Bross T. E., Majerus P. W., Sherman W. R., Tyler A. N., Rubin L. J., Brown J. E. Isolation and characterization of the inositol cyclic phosphate products of polyphosphoinositide cleavage by phospholipase C. Physiological effects in permeabilized platelets and Limulus photoreceptor cells. J Biol Chem. 1985 Nov 5;260(25):13496–13501. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES