Glycolytic oscillation

The problem of modelling glycolytic oscillation has been studied in control theory and dynamical systems since the 1960s since the behaviour depends on the rate of substrate injection. Early models used two variables, but the most complex behaviour they could demonstrate was period oscillations due to the Poincaré–Bendixson theorem, so later models introduced further variables.

Mechanisms and coupling

Glycolytic oscillations are driven by feedback within the glycolytic pathway, where fluctuations in metabolite concentrations synchronize with other cellular processes. These oscillations are tightly coupled with mitochondrial membrane potential, mediated by the ADP/ATP antiporter and the F₀F₁ - ATPase. The ATP/ADP ratio and proton gradients generated by these processes play a central role in this coupling. Experimental evidence shows that inhibitors targeting glycolysis, such as 2-deoxyglucose or iodoacetate, stop both NADH and mitochondrial membrane potential oscillations, highlighting the enzymatic regulation within the glycolytic pathway.

Mathematical models and experimental data further reveal that oscillations in mitochondrial membrane potential are in phase with NADH fluctuations. These synchronized dynamics show how energy metabolism and glycolysis are interconnected, with mitochondrial activity responding to changes in glycolytic flux.