Mathematical modelling of the purine metabolism of the rat liver

Abstract

The regulation of the purine metabolism of the rt liver is studied on the basis of a methematical model which comprises rate laws and kinetic constants of all physiological relevant reactions. The computed stationary and time-dependent concentrations are in a good accordance with experimental data obtained in the ischaemic rat liver and in isolated hepatocytes. In particular, model-based simulations of the adenine nucleotide metabolism have been performed for situations where ATP-deficient states of the cell (hypoxia, anoxia or ischaemia) of various length are followed by onset of ATP production (reoxygenation). These simulations confirm the experimentally observed incomplete recovery of ATP and of the total pool of adenine nucleotides within a few hours of reoxygenation after long-term ATP depletion. Therefore, it can be concluded that this phenomenon is an intrinsic regulatory property of the purine metabolism and not necessarily due to irreversible changes in the activity of the enzymes involved.