Garrison J C, Borland M K
J Biol Chem. 1979 Feb 25;254(4):1129-33.
Experiments were performed to determine if catecholamines can regulate control points in the gluconeogenic pathway, such as mitochondrial pyruvate carboxylation and pyruvate kinase activity, via an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism. Of a number of alpha agonists tested, only norepinephrine, epinephrine, and phenylephrine caused an increase in mitochondrial pyruvate metabolism. The effects of catecholamines on pyruvate carboxylation were not attenuated by 1-propranolol which abolishes changes in cyclic nucleotide levels but were blocked by alpha antagonists such as ergotamine, phenoxybenzamine, and phentolamine. Time course experiments demonstrated that the effects of catecholamines on the mitochondria and on carbohydrate metabolism correlated temporally with the concentration of epinephrine in the medium but not with the small changes in adenosine 3':5'-monophosphate. The effects of catecholamines appeared to require extracellular Ca2+ ion. The observation that catecholamines do not increase gluconeogenesis to the same extent as glucagon was not due to a differential effect on mitochondrial CO2 fixation. Rather, catecholamines caused a smaller inhibition of pyruvate kinase activity than did glucagon. The effects of catecholamines on pyruvate kinase also appeared to be mediated by an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism.
进行了实验以确定儿茶酚胺是否可通过α-肾上腺素能、不依赖3':5'-环磷酸腺苷的机制调节糖异生途径中的控制点，如线粒体丙酮酸羧化作用和丙酮酸激酶活性。在测试的多种α激动剂中，只有去甲肾上腺素、肾上腺素和苯肾上腺素能使线粒体丙酮酸代谢增加。儿茶酚胺对丙酮酸羧化作用的影响不会因可消除环核苷酸水平变化的普萘洛尔而减弱，但会被α拮抗剂如麦角胺、酚苄明和酚妥拉明阻断。时间进程实验表明，儿茶酚胺对线粒体和碳水化合物代谢的影响在时间上与培养基中肾上腺素的浓度相关，但与3':5'-环磷酸腺苷的微小变化无关。儿茶酚胺的作用似乎需要细胞外钙离子。儿茶酚胺不像胰高血糖素那样能同等程度地增加糖异生，这一观察结果并非由于对线粒体二氧化碳固定的不同作用。相反，儿茶酚胺对丙酮酸激酶活性的抑制作用比胰高血糖素小。儿茶酚胺对丙酮酸激酶的作用似乎也由α-肾上腺素能、不依赖3':5'-环磷酸腺苷的机制介导。
