Jacobus W E
Annu Rev Physiol. 1985;47:707-25. doi: 10.1146/annurev.ph.47.030185.003423.
This review has attempted to integrate three areas of cellular bioenergetics to present a novel and comprehensive view of heart high-energy phosphate metabolism. The goal has been to provide a rational view for the functions of phosphocreatine, creatine, and creatine kinase in the energy metabolism of muscle. The first point is that mitochondrial respiratory control is influenced by changes in the concentration of ADP, stimulating the adenine nucleotide translocase and oxidative phosphorylation. Secondly, as a consequence of the proximity of mitochondrial creatine kinase to the translocase, there appears to be a kinetic preference for ADP generated by the forward creatine kinase reaction. As a result, in heart, it can be viewed that the end product of oxidative phosphorylation is phosphocreatine. Finally, thermodynamic considerations suggest that phosphocreatine plays a major role to maintain or buffer the ATP content of the myocardium. Under conditions of increased ATP turnover, large-scale increases in the concentration of ADP, along with major decreases in ATP, are minimized by the creatine kinase equilibrium. The system responds to such a demand with substantial changes in phosphocreatine and creatine, which can kinetically increase the rate of mitochondrial creatine kinase and thus oxidative phosphorylation. Theoretical enzymologists have long argued whether enzymes are under kinetic or thermodynamic control. Heart creatine kinase may be a unique example where both types of control simultaneously operate in different microenvironments, with mitochondrial creatine kinase kinetically controlled, while the sarcoplasmic isozyme is influenced by equilibrium thermodynamics. Overall, heart creatine kinase may be a unique example of "kineto-dynamic" metabolic integration.
本综述试图整合细胞生物能量学的三个领域，以呈现关于心脏高能磷酸代谢的新颖而全面的观点。目的是为磷酸肌酸、肌酸和肌酸激酶在肌肉能量代谢中的功能提供一个合理的观点。第一点是线粒体呼吸控制受ADP浓度变化的影响，刺激腺嘌呤核苷酸转位酶和氧化磷酸化。其次，由于线粒体肌酸激酶与转位酶接近，对于由正向肌酸激酶反应产生的ADP似乎存在动力学偏好。因此，在心脏中，可以认为氧化磷酸化的终产物是磷酸肌酸。最后，热力学考虑表明磷酸肌酸在维持或缓冲心肌ATP含量方面起主要作用。在ATP周转率增加的情况下，ADP浓度的大幅增加以及ATP的大幅减少通过肌酸激酶平衡而最小化。该系统通过磷酸肌酸和肌酸的大量变化来响应这种需求，这可以在动力学上增加线粒体肌酸激酶的速率，从而增加氧化磷酸化的速率。理论酶学家长期以来一直在争论酶是受动力学控制还是受热力学控制。心脏肌酸激酶可能是一个独特的例子，其中两种类型的控制在不同的微环境中同时起作用，线粒体肌酸激酶受动力学控制，而肌浆同工酶受平衡热力学影响。总体而言，心脏肌酸激酶可能是“动力学 - 热力学”代谢整合的一个独特例子。
