A possible mechanism of glycolytic impairment after adenosine triphosphate deplection in the perfused rat heart.

1. When the heart is deprived of substrate and O2 for a long period, the ATP content falls to very low levels, with associated changes in ADP and AMP content, and a fall in intracellular pH. 2. These changes appear sufficient to block the hexokinase reaction, outweighing the normal mechanisms controlling this enzyme. Anaerobic glycolysis then remains blocked, even when glucose supply is restored. The block in anaerobic glycolysis can be overcome, however, by a brief period of oxidative metabolism, apparently because the improvement in adenine nucleotide levels serves to 're-prime' the system. 3. When the cell is severely depleted of ATP, the resulting impairment of glycolysis tends to reinforce the low ATP content, establishing a vicious cycle. Metabolic effects of this kind may cause irreversible loss of function, and may contribute to the mechanism of cell death.