PROPORTIONAL ACTIVATION COEFFICIENTS DURING STIMULATION OF OXIDATIVE-PHOSPHORYLATION BY LACTATE AND PYRUVATE OR BY VASOPRESSIN

A 'proportional activation' approach designed to deal with the influen ce of external effecters within biochemical systems is described. The proportional activation coefficient, which enables the quantitative de termination 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 an d Delta p-consuming subsystems during stimulation of the respiration r ate of cells by a variety of different effecters. Oxidative phosphoryl ation was stimulated by the addition of either lactate and pyruvate (1 0 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 co nsidered to be a specific inhibitor of gluconeogenesis, was found to b lock the Delta p-producing oxidative subsystem as well as the Delta p- consuming subsystem, indicating some nonspecific effects of this inhib itor. Addition of vasopressin to hepatocytes that were incubated in th e presence of lactate and pyruvate resulted in an increase of the resp iratory rate by up to 35%. The relative stimulation of the Delta p-pro ducing and Delta p-consuming subsystems was essentially equal. Using t he 'proportional activation approach' to analyse these and previously published data, it is shown that substrates (lactate/pyruvate and fatt y acids), Ca2+-acting hormones (vasopressin and others) and calcium in muscles (heart muscle and skeletal muscle) activate both subsystems t o a similar extent (it concerns especially Ca2+-dependent systems).