From A H, Petein M A, Michurski S P, Zimmer S D, Uğurbil K
FEBS Lett. 1986 Oct 6;206(2):257-61. doi: 10.1016/0014-5793(86)80992-9.
The mechanism by which mitochondrial respiration is coupled to ATP consumption in intact tissues is unclear. We determined the relationship between high-energy phosphate levels and oxygen consumption rate in rat hearts operating over a range of workloads and perfused with different substrates. With pyruvate +glucose perfusion, ADP levels were in general very low, and varied with MVO2 yielding an apparent Km of 25 +/- 5 microM, suggesting regulation of oxidative phosphorylation through availability of ADP. In contrast, with glucose perfusion in the presence or absence of insulin, ADP levels, ADP/ATP ratio or the phosphate potential were relatively constant over the workload range examined and generally not correlated with alterations in MVO2; it is suggested that under these conditions, carbon substrate delivery to the mitochondria may control mitochondrial respiration. The common feature of both of the suggested regulatory mechanisms is substrate limitation which, however, is exercised at different metabolic points depending on the carbon substrate available to the myocardium.
完整组织中线粒体呼吸与ATP消耗相偶联的机制尚不清楚。我们测定了在一系列工作负荷下运行并用不同底物灌注的大鼠心脏中高能磷酸水平与氧消耗率之间的关系。在丙酮酸+葡萄糖灌注时,ADP水平总体上非常低,并随MVO2变化,表观Km为25±5微摩尔,提示通过ADP的可用性调节氧化磷酸化。相比之下,在有或无胰岛素的情况下进行葡萄糖灌注时,在所研究的工作负荷范围内,ADP水平、ADP/ATP比值或磷酸势相对恒定,且通常与MVO2的变化无关;提示在这些条件下,碳底物向线粒体的输送可能控制线粒体呼吸。两种提出的调节机制的共同特征是底物限制,然而,根据心肌可利用的碳底物,底物限制在不同的代谢点发挥作用。