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. 1987 Aug 15;246(1):139–147. doi: 10.1042/bj2460139

Metabolism of D-myo-inositol 1,3,4,5-tetrakisphosphate by rat liver, including the synthesis of a novel isomer of myo-inositol tetrakisphosphate.

S B Shears 1, J B Parry 1, E K Tang 1, R F Irvine 1, R H Michell 1, C J Kirk 1
PMCID: PMC1148250  PMID: 2823793

Abstract

1. We have studied the metabolism of Ins(1,3,4,5)P4 (inositol 1,3,4,5-tetrakisphosphate) by rat liver homogenates incubated in a medium resembling intracellular ionic strength and pH. 2. Ins(1,3,4,5)P4 was dephosphorylated to a single inositol trisphosphate product, Ins(1,3,4)P3 (inositol 1,3,4-trisphosphate), the identity of which was confirmed by periodate degradation, followed by reduction and dephosphorylation to yield altritol. 3. The major InsP2 (inositol bisphosphate) product was inositol 3,4-bisphosphate [Shears, Storey, Morris, Cubitt, Parry, Michell & Kirk (1987) Biochem. J. 242, 393-402]. Small quantities of a second InsP2 product was also detected in some experiments, but its isomeric configuration was not identified. 4. The Ins(1,3,4,5)P4 5-phosphatase activity was primarily associated with plasma membranes. 5. ATP (5 mM) decreased the membrane-associated Ins(1,4,5)P3 5-phosphatase and Ins(1,3,4,5)P4 5-phosphatase activities by 40-50%. This inhibition was imitated by AMP, adenosine 5'-[beta gamma-imido]triphosphate, adenosine 5'-[gamma-thio]triphosphate or PPi, but not by adenosine or Pi. A decrease in [ATP] from 7 to 3 mM halved the inhibition of Ins(1,3,4,5)P4 5-phosphatase activity, but the extent of inhibition was not further decreased unless [ATP] less than 0.1 mM. 6. Ins(1,3,4,5)P4 5-phosphatase was insensitive to 50 mM-Li+, but was inhibited by 5 mM-2,3-bisphosphoglycerate. 7. The Ins(1,3,4,5)P4 5-phosphatase activity was unchanged by cyclic AMP, GTP, guanosine 5'-[beta gamma-imido]triphosphate or guanosine 5'-[gamma-thio]triphosphate, or by increasing [Ca2+] from 0.1 to 1 microM. 8. Ins(1,3,4)P3 was phosphorylated in an ATP-dependent manner to an isomer of InsP4 that was partially separable on h.p.l.c. from Ins(1,3,4,5)P4. The novel InsP4 appears to be Ins(1,3,4,6)P4. Its metabolic fate and function are not known.

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Selected References

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  1. 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]
  2. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Best L. A role for calcium in the breakdown of inositol phospholipids in intact and digitonin-permeabilized pancreatic islets. Biochem J. 1986 Sep 15;238(3):773–779. doi: 10.1042/bj2380773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brew K., Vanaman T. C., Hill R. L. The role of alpha-lactalbumin and the A protein in lactose synthetase: a unique mechanism for the control of a biological reaction. Proc Natl Acad Sci U S A. 1968 Feb;59(2):491–497. doi: 10.1073/pnas.59.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burgess G. M., McKinney J. S., Fabiato A., Leslie B. A., Putney J. W., Jr Calcium pools in saponin-permeabilized guinea pig hepatocytes. J Biol Chem. 1983 Dec 25;258(24):15336–15345. [PubMed] [Google Scholar]
  7. Connolly T. M., Bansal V. S., Bross T. E., Irvine R. F., Majerus P. W. The metabolism of tris- and tetraphosphates of inositol by 5-phosphomonoesterase and 3-kinase enzymes. J Biol Chem. 1987 Feb 15;262(5):2146–2149. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. Flodgaard H., Torp-Pedersen C. A calcium ion-dependent adenosine triphosphate pyrophosphohydrolase in plasma membrane from rat liver. Demonstration that the adenosine triphosphate analogues adenosine 5'-[betagamma-imido]triphosphate and adenosine 5'-[betagamma-methylene]-triphosphate are substrates for the enzyme. Biochem J. 1978 Jun 1;171(3):817–820. doi: 10.1042/bj1710817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. GRADO C., BALLOU C. E. Myo-inositol phosphates obtained by alkaline hydrolysis of beef brain phosphoinositide. J Biol Chem. 1961 Jan;236:54–60. [PubMed] [Google Scholar]
  13. Guynn R. W., Veloso D., Lawson J. W., Veech R. L. The concentration and control of cytoplasmic free inorganic pyrophosphate in rat liver in vivo. Biochem J. 1974 Jun;140(3):369–375. doi: 10.1042/bj1400369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Heslop J. P., Irvine R. F., Tashjian A. H., Jr, Berridge M. J. Inositol tetrakis- and pentakisphosphates in GH4 cells. J Exp Biol. 1985 Nov;119:395–401. doi: 10.1242/jeb.119.1.395. [DOI] [PubMed] [Google Scholar]
  17. Heyworth C. M., Neumann E. F., Wynn C. H. The stability and aggregation properties of human liver acid beta-D-galactosidase. Biochem J. 1981 Mar 1;193(3):773–779. doi: 10.1042/bj1930773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heyworth C. M., Wallace A. V., Houslay M. D. Insulin and glucagon regulate the activation of two distinct membrane-bound cyclic AMP phosphodiesterases in hepatocytes. Biochem J. 1983 Jul 15;214(1):99–110. doi: 10.1042/bj2140099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. 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]
  22. Irvine R. F., Letcher A. J., Lander D. J., Heslop J. P., Berridge M. J. Inositol(3,4)bisphosphate and inositol(1,3)bisphosphate in GH4 cells--evidence for complex breakdown of inositol(1,3,4)trisphosphate. Biochem Biophys Res Commun. 1987 Feb 27;143(1):353–359. doi: 10.1016/0006-291x(87)90672-3. [DOI] [PubMed] [Google Scholar]
  23. Irvine R. F., Moor R. M. Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem J. 1986 Dec 15;240(3):917–920. doi: 10.1042/bj2400917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Joseph S. K., Williams R. J. Subcellular localization and some properties of the enzymes hydrolysing inositol polyphosphates in rat liver. FEBS Lett. 1985 Jan 28;180(2):150–154. doi: 10.1016/0014-5793(85)81061-9. [DOI] [PubMed] [Google Scholar]
  25. Kirk C. J., Michell R. H., Parry J. B., Shears S. B. Inositol trisphosphate and tetrakisphosphate phosphomonoesterases of rat liver. Biochem Soc Trans. 1987 Feb;15(1):28–32. doi: 10.1042/bst0150028. [DOI] [PubMed] [Google Scholar]
  26. Lim P. E., Tate M. E. The phytases. II. Properties of phytase fractions F 1 and F 2 from wheat bran and the myoinositol phosphates produced by fraction F 2 . Biochim Biophys Acta. 1973 Apr 12;302(2):316–328. doi: 10.1016/0005-2744(73)90160-5. [DOI] [PubMed] [Google Scholar]
  27. Palmer S., Hawkins P. T., Michell R. H., Kirk C. J. The labelling of polyphosphoinositides with [32P]Pi and the accumulation of inositol phosphates in vasopressin-stimulated hepatocytes. Biochem J. 1986 Sep 1;238(2):491–499. doi: 10.1042/bj2380491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Seyfred M. A., Farrell L. E., Wells W. W. Characterization of D-myo-inositol 1,4,5-trisphosphate phosphatase in rat liver plasma membranes. J Biol Chem. 1984 Nov 10;259(21):13204–13208. [PubMed] [Google Scholar]
  29. Shears S. B., Kirk C. J. Characterization of a rapid cellular-fractionation technique for hepatocytes. Application in the measurement of mitochondrial membrane potential in situ. Biochem J. 1984 Apr 15;219(2):375–382. doi: 10.1042/bj2190375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shears S. B., Storey D. J., Morris A. J., Cubitt A. B., Parry J. B., Michell R. H., Kirk C. J. Dephosphorylation of myo-inositol 1,4,5-trisphosphate and myo-inositol 1,3,4-triphosphate. Biochem J. 1987 Mar 1;242(2):393–402. doi: 10.1042/bj2420393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shephard E. H., Hübscher G. Phosphatidate biosynthesis in mitochondrial subfractions of rat liver. Biochem J. 1969 Jun;113(2):429–440. doi: 10.1042/bj1130429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Soboll S., Scholz R., Heldt H. W. Subcellular metabolite concentrations. Dependence of mitochondrial and cytosolic ATP systems on the metabolic state of perfused rat liver. Eur J Biochem. 1978 Jun 15;87(2):377–390. doi: 10.1111/j.1432-1033.1978.tb12387.x. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. TOMLINSON R. V., BALLOU C. E. Myoinositol polyphosphate intermediates in the dephosphorylation of phytic acid by phytase. Biochemistry. 1962 Jan;1:166–171. doi: 10.1021/bi00907a025. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Widnell C. C., Tata J. R. A procedure for the isolation of enzymically active rat-liver nuclei. Biochem J. 1964 Aug;92(2):313–317. doi: 10.1042/bj0920313. [DOI] [PMC free article] [PubMed] [Google Scholar]

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