Roles for hydroxyl groups of D-myo-inositol 1,4,5-trisphosphate in the recognition by its receptor and metabolic enzymes

Masato Hirata, Yutaka Watanabe, Masako Yoshida, Toshitaka Koga, Shoichiro Ozaki

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Positional isomers of D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), Ins(1,4,6)P3, and Ins(1,3,6)P3 were examined to explore the roles for hydroxyl groups of Ins(1,4,5)P3, recognized by metabolic enzymes and by the receptor. Ins(1,4,6)P3 and Ins(1,3,6)P3 inhibited the dephosphorylation of [3H] Ins(1,4,5)P3 by the 5-phosphatase present in erythrocyte ghosts. The Ki value for the former compound was slightly lower than that for Ins(1,4,5)P3, while that for the latter compound was higher. In an assay of [3H] Ins(1,4,5)P3 3-kinase catalyzed by rat brain cytosol, Ins(1,4,6)P3 was as potent as Ins(1,4,5)P3 in inhibiting the phosphorylation, whereas Ins(1,3,6)P3 at concentrations up to 30 μM, was without effect. Ins(1,4,6)P3 and Ins(1,3,6)P3 at higher concentrations were effective in inhibiting [3H]Ins(1,4,5)P3 binding to purified Ins(1,4,5)P3 receptor. It would thus appear that the 2-and 3-hydroxyl groups of Ins(1,4,5)P3 are not primarily involved in recognition by metabolic enzymes, while 6-hydroxyl is slightly or severely involved in recognition by the phosphatase or kinase, respectively. On the other hand, although both 3-OH and 6-OH of Ins(1,4,5)P3 are important in binding by the Ins(1,4,5)P3 receptor to evoke the release of Ca2+, the 6-OH seems to be the more important.

Original languageEnglish
Pages (from-to)19260-19266
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number26
Publication statusPublished - Sep 15 1993

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Inositol 1,4,5-Trisphosphate
Hydroxyl Radical
Phosphoric Monoester Hydrolases
Phosphotransferases
Enzymes
Phosphorylation
Erythrocyte Membrane
Isomers
Cytosol
Rats
Assays
Brain

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Roles for hydroxyl groups of D-myo-inositol 1,4,5-trisphosphate in the recognition by its receptor and metabolic enzymes. / Hirata, Masato; Watanabe, Yutaka; Yoshida, Masako; Koga, Toshitaka; Ozaki, Shoichiro.

In: Journal of Biological Chemistry, Vol. 268, No. 26, 15.09.1993, p. 19260-19266.

Research output: Contribution to journalArticle

Hirata, M, Watanabe, Y, Yoshida, M, Koga, T & Ozaki, S 1993, 'Roles for hydroxyl groups of D-myo-inositol 1,4,5-trisphosphate in the recognition by its receptor and metabolic enzymes', Journal of Biological Chemistry, vol. 268, no. 26, pp. 19260-19266.
Hirata, Masato ; Watanabe, Yutaka ; Yoshida, Masako ; Koga, Toshitaka ; Ozaki, Shoichiro. / Roles for hydroxyl groups of D-myo-inositol 1,4,5-trisphosphate in the recognition by its receptor and metabolic enzymes. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 26. pp. 19260-19266.
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abstract = "Positional isomers of D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), Ins(1,4,6)P3, and Ins(1,3,6)P3 were examined to explore the roles for hydroxyl groups of Ins(1,4,5)P3, recognized by metabolic enzymes and by the receptor. Ins(1,4,6)P3 and Ins(1,3,6)P3 inhibited the dephosphorylation of [3H] Ins(1,4,5)P3 by the 5-phosphatase present in erythrocyte ghosts. The Ki value for the former compound was slightly lower than that for Ins(1,4,5)P3, while that for the latter compound was higher. In an assay of [3H] Ins(1,4,5)P3 3-kinase catalyzed by rat brain cytosol, Ins(1,4,6)P3 was as potent as Ins(1,4,5)P3 in inhibiting the phosphorylation, whereas Ins(1,3,6)P3 at concentrations up to 30 μM, was without effect. Ins(1,4,6)P3 and Ins(1,3,6)P3 at higher concentrations were effective in inhibiting [3H]Ins(1,4,5)P3 binding to purified Ins(1,4,5)P3 receptor. It would thus appear that the 2-and 3-hydroxyl groups of Ins(1,4,5)P3 are not primarily involved in recognition by metabolic enzymes, while 6-hydroxyl is slightly or severely involved in recognition by the phosphatase or kinase, respectively. On the other hand, although both 3-OH and 6-OH of Ins(1,4,5)P3 are important in binding by the Ins(1,4,5)P3 receptor to evoke the release of Ca2+, the 6-OH seems to be the more important.",
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