关于Ca2+与丙酮酸在调节大鼠心脏丙酮酸脱氢酶活性中的相互作用的研究。饥饿和糖尿病的影响。

Studies on the interactions of Ca2+ and pyruvate in the regulation of rat heart pyruvate dehydrogenase activity. Effects of starvation and diabetes.

作者信息

McCormack J G, Edgell N J, Denton R M

出版信息

Biochem J. 1982 Feb 15;202(2):419-27. doi: 10.1042/bj2020419.

DOI:10.1042/bj2020419

PMID:7092823

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1158126/

Abstract

Previous studies showed that the activation of pyruvate dehydrogenase within intact rat heart mitochondria of pyruvate is much diminished in mitochondria from starved or diabetic animals [see Kerbey, Randle, Cooper, Whitehouse, Pask & Denton (1976) Biochem. J. 154, 327-348]. In the present study, diminished responses to added Ca2+ and ADP were also found in these mitochondria. 2. Starvation or diabetes did not affect the mitochondrial respiratory control ratio of the ATP content. Moreover, starvation and diabetes did not alter the response of the intramitochondrial Ca2+-sensitive enzyme, 2-oxoglutarate dehydrogenase, to changes in the extramitochondrial concentration of Ca2+ and 2-oxoglutarate, thus indicating that there were no appreciable changes in the distribution of Ca2+ and H+ across the mitochondrial inner membrane. 3. Pyruvate, Ca2+ and ADP were found to have synergistic effects on pyruvate dehydrogenase activity, particularly in mitochondria from starved and diabetic rats. 4. The results suggest that the effects of diabetes and starvation on pyruvate dehydrogenase are not brought about by changes in the distribution of these effectors across the mitochondrial inner membrane or by changes in the intrinsic sensitivity of the kinase or phosphatase of the pyruvate dehydrogenase system to pyruvate, Ca2+ or ADP; rather it is probably that there is an increase in the maximum activity of kinase relative to that of the phosphatase. 6. The results also lend further support to the hypothesis that adrenaline may bring about the activation of pyruvate dehydrogenase in the rat heart by an increase in the intramitochondrial concentration of Ca2+.

摘要

先前的研究表明，在饥饿或糖尿病动物的线粒体中，完整大鼠心脏线粒体中丙酮酸脱氢酶对丙酮酸的激活作用显著减弱[见Kerbey、Randle、Cooper、Whitehouse、Pask和Denton（1976年），《生物化学杂志》154卷，327 - 348页]。在本研究中，还发现这些线粒体对添加的Ca²⁺和ADP的反应减弱。2. 饥饿或糖尿病不影响线粒体呼吸控制率或ATP含量。此外，饥饿和糖尿病不会改变线粒体内Ca²⁺敏感酶2 - 氧代戊二酸脱氢酶对线粒体外Ca²⁺和2 - 氧代戊二酸浓度变化的反应，因此表明Ca²⁺和H⁺在线粒体内膜两侧的分布没有明显变化。3. 发现丙酮酸、Ca²⁺和ADP对丙酮酸脱氢酶活性有协同作用，特别是在饥饿和糖尿病大鼠的线粒体中。4. 结果表明，糖尿病和饥饿对丙酮酸脱氢酶的影响不是由这些效应物在线粒体内膜两侧的分布变化或丙酮酸脱氢酶系统的激酶或磷酸酶对丙酮酸、Ca²⁺或ADP的内在敏感性变化引起的；相反，可能是激酶的最大活性相对于磷酸酶有所增加。6. 这些结果也进一步支持了这样的假设，即肾上腺素可能通过增加线粒体内Ca²⁺浓度来激活大鼠心脏中的丙酮酸脱氢酶。