AJP - Heart and Circulatory Physiology, Vol 232, Issue 4 386-H393, Copyright © 1977 by American Physiological Society
Computer simulation of ischemic rat heart purine metabolism. I. Model construction
M. C. Kohn and D. Garfinkel
A model is proposed for the partial depletion of the adenine nucleotide
pool in the ischemic perfused rat heart which involves seven enzymes:
adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase,
adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and
inorganic pyrophosphatase. The computer implementation of this model is in
terms of rate laws, several of which were obtained by a systematic
least-squares fitting procedure. Depletion of the adenine nucleotide pool
is initiated by the release of endogenous noradrenaline into the
interstitial fluid, which results from a fall in tissue PO2, and the
subsequent activation of adenylate cyclase. In this model the substrate for
5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of
extracellular fluid and functions as a vasodilator; excess adenosine is
incorporated into the tissue by a "permease" with Michaelis-Menten kinetics
and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms,
such as the deamination of AMP by adenylate deaminase and conversion of AMP
to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative
biochemical grounds.
