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CELLULAR METABOLISM

Linear relation between time constant of oxygen uptake kinetics, total creatine, and mitochondrial content in vitro

¹Department of Kinesiology, Arizona State University, Tempe, Arizona; and ²Department of Kinesiology, Kansas State University, Manhattan, Kansas

Submitted 3 April 2007 ; accepted in final form 11 October 2007

Following the onset of moderate aerobic exercise, the rate of oxygen consumption (J_o) rises monoexponentially toward the new steady state with a time constant () in the vicinity of 30 s. The mechanisms underlying this delay have been studied over several decades. Meyer's electrical analog model proposed the concept that the is given by = R_m·C, where R_m is mitochondrial resistance to energy transfer, and C is metabolic capacitance, determined primarily by the cellular total creatine pool (TCr = phosphocreatine + creatine). The purpose of this study was to evaluate in vitro the J_o kinetics of isolated rat skeletal muscle mitochondria at various levels of TCr and mitochondrial protein. Mitochondria were incubated in a medium containing 5.0 mM ATP, TCr pools of 0–1.5 mM, excess creatine kinase, and an ATP-splitting system of glucose + hexokinase (HK). Pyruvate and malate (1 mM each) were present as oxidative substrates. J_o was measured across time after HK was added to elicit one of two levels of J_o (40 and 60% of state 3). At TCr levels (in mM) of 0.1, 0.2, 0.3, 0.75, and 1.5, the corresponding values (s, means ± SE) were 22.2 ± 3.0, 36.3 ± 2.2, 65.7 ± 4.3, 168.1 ± 22.2, and 287.3 ± 25.9. Thus increased linearly with TCr (R² = 0.916). Furthermore, the experimentally observed varied linearly and inversely with the mitochondrial protein added. These in vitro results consistently conform to the predictions of Meyer's electrical analog model.

mitochondrial resistance; hexokinase; creatine kinase