Korzeniewski Bernard, Zoladz Jerzy A
Institute of Molecular Biology and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Kraków, Poland.
Biochem J. 2004 May 1;379(Pt 3):703-10. doi: 10.1042/BJ20031740.
Using a computer model of oxidative phosphorylation developed previously [Korzeniewski and Mazat (1996) Biochem. J. 319, 143-148; Korzeniewski and Zoladz (2001) Biophys. Chem. 92, 17-34], we analyse the effect of several factors on the oxygen-uptake kinetics, especially on the oxygen consumption rate (VO2) and half-transition time t(1/2), at the onset of exercise in skeletal muscles. Computer simulations demonstrate that an increase in the total creatine pool [PCr+/-Cr] (where Cr stands for creatine and PCr for phosphocreatine) and in glycolytic ATP supply lengthen the half-transition time, whereas increase in mitochondrial content, in parallel activation of ATP supply and ATP usage, in oxygen concentration, in proton leak, in resting energy demand, in resting cytosolic pH and in initial alkalization decrease this parameter. Theoretical studies show that a decrease in the activity of creatine kinase (CK) [displacement of this enzyme from equilibrium during on-transient (rest-to-work transition)] accelerates the first stage of the VO2 on-transient, but slows down the second stage of this transient. It is also demonstrated that a prior exercise terminated a few minutes before the principal exercise shortens the transition time. Finally, it is shown that at a given ATP demand, and under conditions where CK works near the thermodynamic equilibrium, the half-transition time of VO2 kinetics is determined by the amount of PCr that has to be transformed into Cr during rest-to-work transition; therefore any factor that diminishes the difference in [PCr] between rest and work at a given energy demand will accelerate the VO2 on-kinetics. Our conclusions agree with the general idea formulated originally by Easterby [(1981) Biochem. J. 199, 155-161] that changes in metabolite concentrations determine the transition times between different steady states in metabolic systems.
利用先前建立的氧化磷酸化计算机模型[科尔泽涅夫斯基和马扎特（1996年）《生物化学杂志》319卷，第143 - 148页；科尔泽涅夫斯基和佐拉德（2001年）《生物物理化学》92卷，第17 - 34页]，我们分析了几个因素对骨骼肌运动开始时氧摄取动力学的影响，特别是对氧消耗率（VO2）和半转换时间t(1/2)的影响。计算机模拟表明，总肌酸池[PCr +/ - Cr]（其中Cr代表肌酸，PCr代表磷酸肌酸）和糖酵解ATP供应的增加会延长半转换时间，而线粒体含量的增加、ATP供应与ATP利用的并行激活、氧浓度、质子泄漏、静息能量需求、静息胞质pH值以及初始碱化的增加会降低该参数。理论研究表明，肌酸激酶（CK）活性的降低[在从静息到工作的转换过程中该酶偏离平衡状态]会加速VO2从静息到工作转换的第一阶段，但会减缓该转换的第二阶段。还表明，在主要运动前几分钟终止的先前运动可缩短转换时间。最后表明，在给定的ATP需求下，以及在CK接近热力学平衡工作的条件下，VO2动力学的半转换时间由从静息到工作转换过程中必须转化为Cr的PCr量决定；因此，在给定能量需求下，任何减少静息和工作时[PCr]差异的因素都会加速VO2的从静息到工作的动力学过程。我们的结论与伊斯特比最初提出的总体观点一致[(1981年)《生物化学杂志》199卷，第155 - 161页]，即代谢物浓度的变化决定了代谢系统中不同稳态之间的转换时间。
