First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and phosphorylcreatine level. Implications for the control of respiration.
In frog sartorius muscle, after a tetanus at 20 degrees C, during which an impulse-like increase occurs in the rate of ATP hydrolysis, the rate of O2 consumption (QO2) reaches a peak relatively quickly and then declines monoexponentially, with a time constant not dependent on the tetanus duration (tau = 2.6 min in Rana pipiens and 2.1 min in Rana temporaria). To a good approximation, these kinetics are those of a first-order impulse response, and the scheme of reactions that couple O2 consumption to extramitochondrial ATP hydrolysis thus behaves as a first-order system. It is first deduced and then demonstrated directly that while QO2(t) is monoexponential, it changes in parallel with the levels of creatine and phosphorylcreatine, with proportionality constants +/- 1/tau p, where p is the P/O2 ratio in vivo. From this, it is further deduced that the mitochondrial creatine kinase (CK) reaction is pseudo-first order in vivo. The relationship between [creatine] and QO2 predicted by published models of the control of respiration is markedly different from that actually observed. As shown here, the first-order kinetics of QO2 are consistent with the hypothesis that respiration is rate-limited by the mitochondrial CK reaction; this has as a corollary the "creatine shuttle" hypothesis.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003401:Creatine / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism; D007700:Kinetics; D008931:Mitochondria, Muscle / Q000378:metabolism; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism* / Q000502:physiology; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism*; D011898:Ranidae / Q000378:metabolism*; D013997:Time Factors
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D003401:Creatine