MULTIPLE CONTROLS OF OXIDATIVE-METABOLISM IN LIVING TISSUES AS STUDIED BY PHOSPHORUS MAGNETIC-RESONANCE
MULTIPLE CONTROLS OF OXIDATIVE-METABOLISM IN LIVING TISSUES AS STUDIED BY PHOSPHORUS MAGNETIC-RESONANCE
复制标题
DOI：
10.1073/pnas.83.24.9458
复制
发表时间：
1986-12-01
影响因子：
11.1
通讯作者：
GRAHAM, T
中科院分区：
文献类型：
--
作者：
CHANCE, B;LEIGH, JS;GRAHAM, T
在已用磷磁共振波谱研究的各种组织中，观察到氧化代谢的三种代谢控制。控制骨骼肌氧化代谢的主要途径是ADP(或PI/磷酸肌酸)。这一结论是基于对人体在稳态运动过程中手臂肌肉的研究得出的。工作成本(Vm与PI/磷酸肌酸)符合Michaelis-Menten矩形双曲线，其中Km值从0.5到0.6，Vmax值从50到200(在几乎恒定的pH下)在方程V/Vmax=1/(1+0.6磷酸肌酸/PI)的线性化曲线图中找到，其中V是工作水平(其等于酶反应的速度)，Vmax是最大功容量，其是氧化代谢的酶活性(E)的量度。对运动的适应会增加工作-成本关系的斜率，并导致Vmax或E的巨大变化。第二次代谢控制可能会增加工作-成本关系的斜率，但不会增加Vmax。例如，运动的开始可以导致改善的特征，这可以用增加2倍的底物输送来解释，例如，通过微循环控制增加氧气输送。成年犬的心脏组织提供了一个最佳耐力表现适应的例子，并表现出所观察到的最陡峭的工作-成本关系，这归因于对底物输送的协调控制，这可能涉及到钙离子和无机磷对NADH的控制；也可能涉及对O2输送的控制。计算出的工作-成本关系与在小猎犬心脏上观察到的相似。理论曲线表明，多重控制的易感性是在多重控制范围结束时代谢控制的急剧转折点--这可能是在高V/Vmax时心功能不稳定的原因。
Three types of metabolic control of oxidative metabolism are observed in the various tissues that have been studied by phosphorous magnetic resonance spectroscopy. The principal control of oxidative metabolism in skeletal muscle is by ADP (or Pi/phosphocreatine). This conclusion is based upon studies of arm muscles of humans during steady-state exercise. A work-cost (Vm vs. Pi/phosphocreatine) relationship follows a Michaelis-Menten rectangular hyperbola, where Km values from 0.5 to 0.6 and Vmax values from 50 to 200 (at nearly constant pH) are found in linearized plots of the equation V/Vmax = 1/(1 + 0.6 phosphocreatine/Pi) where V is work level (which is equal to the velocity of the enzymatic reaction) and Vmax is the maximal work capacity that is a measure of the enzyme activity (E) of oxidative metabolism. Adaptation to exercise enhances the slope of the work-cost relationship and causes large changes in Vmax or E. A second metabolic control may enhance the slope of the work-cost relationship but not Vmax. For example, the initiation of exercise can lead to an improved characteristic that can be explained by 2-fold increased substrate delivery, for example, increased oxygen delivery by microcirculatory control. Cardiac tissue of the adult dog affords an example of optimal endurance performance adaptation and exhibits the steepest work-cost relationship observed and is attributed to a coordinated control of substrate delivery that may involve Ca2+ and inorganic phosphate control of NADH; control of O2 delivery may also be involved. The calculated work-cost relationship is simlar to that observed in the beagle heart. The theoretical curve illustrates that the liability of multiple controls is a sharp break point in metabolic control at the end of the multiple control range-a possible cause of instability of cardiac performance at high V/Vmax.