In vivo control of phosphofructokinase: system models suggest new experimental protocols

Abstract

There is still uncertainty as to how much control of in vivo rates of glycolysis by phosphofructokinase (PFK) depends on cytosolic phosphate energy state. Three models of PFK kinetics incorporating sensitivity to pH, adenine nucleotides, and inorganic phosphate (Pi) were embedded in the physiological "phosphate energy system" of creatine-containing tissues [Connett, R.J. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949-R959, 1988]. Effects of changes in phosphate energy state and total adenine nucleotide and phosphate pools on steady-state kinetics were examined. Analyses mimicking in vitro experiments indicated no activity at the pH and [ATP] of working muscles. When tested using the coordinated changes in Pi and adenine nucleotides expected in vivo, all models showed reasonable activity. Control was dominated by [Pi] in the normal physiological range of energy states. The almost linear response to phosphate energy state, measured by creatine charge (phosphocreatine/total creatine), is insensitive to the absolute size of the adenine nucleotide pool. A step to almost full activation occurred when phosphocreatine buffering of [ATP] was exceeded. Several experimental studies are suggested.