Wanders R J, Groen A K, Van Roermund C W, Tager J M
Eur J Biochem. 1984 Jul 16;142(2):417-24. doi: 10.1111/j.1432-1033.1984.tb08303.x.
The control exerted by the adenine nucleotide translocator and the ADP-regenerating system on oxidative phosphorylation was studied in isolated rat-liver mitochondria respiring with succinate. At intermediate rates of respiration the flux control coefficient (control strength) of the adenine nucleotide translocator on respiration was much higher with creatine/creatine kinase than with glucose/hexokinase as the ADP-regenerating system. In contrast, at the same rate of respiration the flux control coefficient of creatine kinase was much lower than that of hexokinase. On addition of a small amount of carboxyatractyloside to mitochondria respiring in the presence of glucose/hexokinase or creatine/creatine kinase, the rate of respiration decreased abruptly and then increased again to a new steady state which was lower with creatine/creatine kinase than with glucose/hexokinase. In the new steady state, the extramitochondrial ATP/ADP ratio was lower with glucose/hexokinase than with creatine/creatine kinase. At the same rate of respiration, the elasticity coefficient of creatine kinase towards the extramitochondrial ATP/ADP ratio was much higher than that of hexokinase. The connectivity theorem [Kacser, H. and Burns, J.A. (1973) in Rate Control of Biological Processes (Davies, D.D., ed.) pp. 65-104, Cambridge University Press, London] which relates the flux control coefficients of two adjacent enzymes to their elasticity coefficients towards the common intermediate, provides an explanation for the difference in flux control coefficient of the adenine nucleotide translocator with the two ADP-regenerating systems. Using principles developed by R. Heinrich and T.A. Rapoport [BioSystems 7, 130-136 (1975)], the flux control coefficients of the adenine nucleotide translocator and hexokinase on phosphorylation were also calculated from the elasticity coefficients of these enzymes towards the extramitochondrial ATP/ADP ratio and the controls exerted by these enzymes on the extramitochondrial ATP/ADP ratio. The calculated values were approximately 30% lower than the values measured directly. The elasticity coefficient of the adenine nucleotide translocator towards the extramitochondrial ATP/ADP ratio was determined, using either the connectivity theorem of Kacser and Burns (loc. cit.) or a new connectivity theorem developed by Westerhoff (following paper in this journal). Good agreement was obtained using the different methods of calculation.(ABSTRACT TRUNCATED AT 400 WORDS)
在以琥珀酸为呼吸底物的离体大鼠肝脏线粒体中，研究了腺嘌呤核苷酸转位酶和ADP再生系统对氧化磷酸化的调控作用。在中等呼吸速率下，以肌酸/肌酸激酶作为ADP再生系统时，腺嘌呤核苷酸转位酶对呼吸的通量控制系数（控制强度）比以葡萄糖/己糖激酶作为ADP再生系统时高得多。相反，在相同呼吸速率下，肌酸激酶的通量控制系数比己糖激酶低得多。向在葡萄糖/己糖激酶或肌酸/肌酸激酶存在下呼吸的线粒体中添加少量羧基苍术苷后，呼吸速率突然下降，然后再次上升至新的稳定状态，以肌酸/肌酸激酶为底物时的稳定状态低于以葡萄糖/己糖激酶为底物时的稳定状态。在新的稳定状态下，以葡萄糖/己糖激酶为底物时线粒体外ATP/ADP比值低于以肌酸/肌酸激酶为底物时的比值。在相同呼吸速率下，肌酸激酶对线粒体外ATP/ADP比值的弹性系数比己糖激酶高得多。将两个相邻酶的通量控制系数与其对共同中间物的弹性系数相关联的连通性定理[Kacser, H.和Burns, J.A.（1973年），载于《生物过程的速率控制》（Davies, D.D.主编），第65 - 104页，剑桥大学出版社，伦敦]，解释了腺嘌呤核苷酸转位酶在两种ADP再生系统下通量控制系数的差异。利用R. Heinrich和T.A. Rapoport提出的原理[《生物系统》7, 130 - 136（1975年）]，还根据腺嘌呤核苷酸转位酶和己糖激酶对线粒体外ATP/ADP比值的弹性系数以及这些酶对线粒体外ATP/ADP比值的调控作用，计算了它们对磷酸化的通量控制系数。计算值比直接测量值低约30%。使用Kacser和Burns（同处）的连通性定理或Westerhoff提出的新连通性定理（本期刊后续论文），测定了腺嘌呤核苷酸转位酶对线粒体外ATP/ADP比值的弹性系数。不同计算方法得到了很好的一致性。（摘要截断于400字）
