AJP - Regulatory, Integrative and Comparative Physiology, Vol 257, Issue 4 878-R888, Copyright © 1989 by American Physiological Society
In vivo control of phosphofructokinase: system models suggest new experimental protocols
R. J. Connett
Department of Physiology, School of Medicine and Dentistry, University of Rochester, New York 14642.
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.
