First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and phosphorylcreatine level. Implications for the control of respiration.

Abstract

In frog sartorius muscle, after a tetanus at 20.degree. 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 R. temporaria). To a good approximation, these kinetics are those of a 1st-order impulse response, and the scheme of reactions that couple O2 consumption to extramitochondrial ATP hydrolysis thus behaves as a 1st-order system. 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. The mitochondrial creatine kinase (CK) reaction is pseudo-1st 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 1st-order kinetcis 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.