Connolly T M, Wilson D B, Bross T E, Majerus P W
J Biol Chem. 1986 Jan 5;261(1):122-6.
The phosphoinositides are metabolized by phospholipase C in response to hormone or agonist stimulation in many cell types to produce diglyceride and water-soluble inositol phosphates. We have recently shown that the phospholipase C reaction products include cyclic phosphate esters of inositol. One of these, inositol 1, 2-cyclic 4,5-trisphosphate, is active in promoting Ca2+ mobilization in platelets and in inducing changes in conductance in Limulus photoreceptors similar to those produced by light (Wilson, D. B., Connolly, T. M., Bross, T. E., Majerus, P. W., Sherman, W. R., Tyler, A., Rubin, L. J., and Brown, J. E. (1985) J. Biol. Chem. 260, 13496-13501. In the current study, we have examined the metabolism of the inositol phosphates. We find that both cyclic and non-cyclic inositol trisphosphates are metabolized by inositol 1,4,5-trisphosphate 5-phosphomonoesterase, to inositol 1,2-cyclic bisphosphate and inositol 1,4-bisphosphate, respectively. However, the apparent Km of the enzyme for the cyclic substrate is approximately 10-fold higher than for the non-cyclic substrate. These inositol bisphosphates are more slowly degraded to inositol 1,2-cyclic phosphate and inositol 1-phosphate, respectively. Inositol 1,2-cyclic phosphate is then hydrolyzed to inositol 1-phosphate, which in turn is degraded to inositol and inorganic phosphate by inositol 1-phosphate phosphatase. The human platelet inositol 1,2-cyclic phosphate hydrolase enzyme and a similar rat kidney hydrolase do not utilize the cyclic polyphosphate esters of inositol as substrates. These results suggest that the inositol cyclic phosphates and the non-cyclic inositol phosphates are metabolized separately by phosphatases to cyclic and non-cyclic inositol monophosphates. The cyclic monophosphate is then converted to inositol 1-phosphate by a cyclic hydrolase. We suggest that the enzymes that metabolize the inositol phosphates may serve to regulate cellular responses to these compounds.
在许多细胞类型中，磷酸肌醇在激素或激动剂刺激下被磷脂酶C代谢，产生甘油二酯和水溶性肌醇磷酸。我们最近发现，磷脂酶C反应产物包括肌醇的环磷酸酯。其中之一，肌醇1,2-环4,5-三磷酸，在促进血小板中Ca2+动员以及诱导鲎光感受器中电导变化方面具有活性，类似于光产生的变化（威尔逊，D.B.，康诺利，T.M.，布罗斯，T.E.，马杰鲁斯，P.W.，谢尔曼，W.R.，泰勒，A.，鲁宾，L.J.，以及布朗，J.E.（1985年）《生物化学杂志》260，13496 - 13501）。在当前研究中，我们研究了肌醇磷酸的代谢。我们发现，环状和非环状肌醇三磷酸都被肌醇1,4,5-三磷酸5-磷酸单酯酶代谢，分别生成肌醇1,2-环二磷酸和肌醇1,4-二磷酸。然而，该酶对环状底物的表观Km值比对非环状底物大约高10倍。这些肌醇二磷酸分别更缓慢地降解为肌醇1,2-环磷酸和肌醇1-磷酸。然后肌醇1,2-环磷酸被水解为肌醇1-磷酸，肌醇1-磷酸又通过肌醇1-磷酸磷酸酶降解为肌醇和无机磷酸。人血小板肌醇1,2-环磷酸水解酶和一种类似的大鼠肾脏水解酶不将肌醇的环多磷酸酯用作底物。这些结果表明，肌醇环磷酸酯和非环状肌醇磷酸通过磷酸酶分别代谢为环状和非环状肌醇单磷酸。然后环状单磷酸通过一种环水解酶转化为肌醇1-磷酸。我们认为，代谢肌醇磷酸的酶可能有助于调节细胞对这些化合物的反应。
