AJP - Cell Physiology, Vol 258, Issue 6 C995-1005, Copyright © 1990 by American Physiological Society
A simple model of aerobic metabolism: applications to work transitions in muscle
C. I. Funk, A. Clark Jr and R. J. Connett
Department of Mechanical Engineering, University of Rochester, New York 14627.
Adding kinetics to the model of the phosphate energy system [Connett. Am.
J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949-R959,
1988], we provide a framework for analyzing metabolic transients in muscle
tissue. We modify the formalism of the earlier model and introduce a
buffering factor, which measures buffering of adenine nucleotides by
phosphocreatine. The time course of the phosphate energy state can be
calculated given the following: 1) adenosinetriphosphatase (ATPase) rate,
2) pH, and 3) a mitochondrial driving function, i.e., ATP production in
terms of the phosphate energy state. We use mitochondrial driving functions
derived from steady-state measurements to predict the time courses for
rest-work transitions. Predictions for transitions in the rat gastrocnemius
muscle agree with published values. The model is used to test different
existing hypotheses of oxygen consumption (VO2) regulation. Each hypothesis
generates a specific mitochondrial driving function, which in turn
generates a specific time course of phosphate energy state during
transitions. A mitochondrial driving function based on enzyme kinetics with
ADP as a substrate leads to time courses not matching the data.
Mitochondrial driving functions that are linear with phosphocreatine, Pi,
phosphorylation potential, or the pool of high-energy phosphate bonds
(phosphate potential energy) gave good agreement with the data.
