ANALYSIS OF THE CONTROL OF RESPIRATION RATE, PHOSPHORYLATION RATE, PROTON LEAK RATE AND PROTONMOTIVE FORCE IN ISOLATED-MITOCHONDRIA USING THE TOP-DOWN APPROACH OF METABOLIC CONTROL-THEORY
ANALYSIS OF THE CONTROL OF RESPIRATION RATE, PHOSPHORYLATION RATE, PROTON LEAK RATE AND PROTONMOTIVE FORCE IN ISOLATED-MITOCHONDRIA USING THE TOP-DOWN APPROACH OF METABOLIC CONTROL-THEORY
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DOI：
10.1111/j.1432-1033.1990.tb15405.x
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发表时间：
1990-03-10
期刊：
影响因子：
--
通讯作者：
BRAND, MD
中科院分区：
文献类型：
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作者：
HAFNER, RP;BROWN, GC;BRAND, MD
通过加入寡霉素或ADP再生系统（葡萄糖和不同量的己糖激酶），将分离的线粒体的呼吸速率设定为不同的值。我们测量了呼吸速率和膜电位之间的关系，呼吸是通过在每种条件下加入丙二酸滴定。我们利用代谢控制理论中的通量控制求和定理、连通性定理和分支定理，计算了呼吸链（及相关反应）、磷酸化系统（及相关反应）和质子泄漏对呼吸速率的控制。分析还得到了这三个反应对磷酸化速率和质子漏率的通量控制系数以及对质子动力的浓度控制系数。我们发现，呼吸速率在很大程度上是由非磷酸化条件下的质子泄漏，由磷酸化系统在中间速率和磷酸化系统和呼吸链在状态3控制。磷酸化的速率主要由磷酸化系统本身在状态4和中间速率控制，而状态3控制在磷酸化系统和呼吸链之间共享;质子泄漏具有不显著的控制。在所有状态下，磷酸化系统对质子泄漏有较大的负控制;链和质子泄漏都有较大的正控制系数。质子动力由链和磷酸化系统控制，质子泄漏几乎没有控制。
The rate of respiration of isolated mitochondria was set at different values by addition of either oligomycin or an ADP-regenerating system (glucose and different amounts of hexokinase). We measured the relationship between respiration rate and membrane potential as respiration was titrated by the addition of malonate under each condition. We used the flux control summation and connectivity theorems and the branching theorem of metabolic control theory to calculate the control over respiration rate exerted by the respiratory chain (and associated reactions), phosphorylating system (and association reactions) and proton leak at each respiration rate. The analysis also yielded the flux control coefficients of these three reactions over phosphorylation rate and proton leak rate and their concentration control coefficients over protonmotive force. We found that respiration rate was controlled largely by the proton leak under non-phosphorylating conditions, by the phosphorylating system at intermediate rates and by both the phosphorylating system and the respiratory chain in state 3. The rate of phosphorylation was controlled largely by the phosphorylating system itself in state 4 and at intermediate rates, while state 3 control was shared between the phosphorylating system and the respiratory chain; the proton leak had insignificant control. In all states the phosphorylating system had large negative control over the proton leak; the chain and the proton leak both had large positive control coefficients. The protonmotive force was controlled by the chain and by the phosphorylating system; the proton leak had little control.