Proportional activation coefficients during stimulation of oxidative phosphorylation by lactate and pyruvate or by...

A 'proportional activation' approach designed to deal with the influence of external effectors within biochemical systems is described. The proportional activation coefficient, which enables the quantitative determination of the relative stimulation of different parts of a system by a given effector, is defined. The proportional activation approach was used to calculate the relative activation of delta p-producing and delta p-consuming subsystems during stimulation of the respiration rate of cells by a variety of different effectors. Oxidative phosphorylation was stimulated by the addition of either lactate and pyruvate (10 mM and 1 mM) or vasopressin. The addition of lactate and pyruvate to suspensions of resting hepatocytes increased the respiration rate by about 50%. The delta p-consuming subsystem was stimulated about 60% as much as the delta p-producing subsystem. Quinolinic acid, commonly considered to be a specific inhibitor of gluconeogenesis, was found to block the delta p-producing oxidative subsystem as well as the delta p-consuming subsystem, indicating some nonspecific effects of this inhibitor. Addition of vasopressin to hepatocytes that were incubated in the presence of lactate and pyruvate resulted in an increase of the respiratory rate by up to 35%. The relative stimulation of the delta p-producing and delta p-consuming subsystems was essentially equal. Using the 'proportional activation approach' to analyse these and previously published data, it is shown that substrates (lactate/pyruvate and fatty acids), Ca(2+)-acting hormones (vasopressin and others) and calcium in muscles (heart muscle and skeletal muscle) activate both subsystems to a similar extent (it concerns especially Ca(2+)-dependent systems).