AJP - Regulatory, Integrative and Comparative Physiology, Vol 232, Issue 5 175-R184, Copyright © 1977 by American Physiological Society
Computer simulation of rat heart metabolism after adding glucose to the perfusate
M. J. Achs and D. Garfinkel
An experiment where perfused rat hearts receiving no substrate are suddenly
given glucose with insulin in the perfusate is simulated with a computer
model of cardiac energy metabolism. Mitochondrial metabolism is
quantitatively reorganized under cytoplasmic control, with fatty acid
oxidation undergoing a two-step decrease. There is an unspanning of the
Krebs cycle (different reactions going at different rates) due primarily to
slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic
glucose reaches a new steady state. Mitochondria in vitro are known to have
higher pH than their surroundings; it is found here that this also holds in
situ. Under these conditions, glycolysis is coherently substrate
controlled, as is phosphofructokinase, usually considered the typical
example of an allosteric enzyme. Limitations on simple methods of analyzing
metabolic data of this type, e.g., use of lactate/pyruvate ratios to
calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and
other biochemical information has been integrated into a physiologically
meaningful system.
