In
biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
, a glycolytic oscillation is the repetitive fluctuation of in the concentrations of
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s,
classically observed experimentally in yeast and muscle. The first observations of oscillatory behaviour in glycolysis were made by Duysens and Amesz in 1957. Glycolytic oscillations are typically induced in dense suspensions of cells exposed to glucose under anaerobic or semi- anaerobic conditions.
The problem of modelling glycolytic oscillation has been studied in
control theory
Control theory is a field of control engineering and applied mathematics that deals with the control system, control of dynamical systems in engineered processes and machines. The objective is to develop a model or algorithm governing the applic ...
and
dynamical systems
In mathematics, a dynamical system is a system in which a Function (mathematics), function describes the time dependence of a Point (geometry), point in an ambient space, such as in a parametric curve. Examples include the mathematical models ...
since the 1960s
since the behaviour depends on the rate of
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (aquatic environment), the earthy material that exi ...
injection.
Early models used two variables, but the most complex behaviour they could demonstrate was period oscillations due to the
Poincaré–Bendixson theorem
In mathematics, the Poincaré–Bendixson theorem is a statement about the long-term behaviour of orbits of continuous dynamical systems on the plane, cylinder, or two-sphere.
Theorem
Given a differentiable real dynamical system defined on an op ...
, 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 F
0F
1 - 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.
Role of intracellular ions
Potassium (K
+) is essential for glycolytic oscillations, with intracellular K
+ concentrations oscillating in phase with NADH, ATP, and mitochondrial membrane potential. Mutants lacking K
+ transporters, such as the mitochondrial K
+/H
+ exchanger Mdm38p or the endosomal Nhx1p, fail to exhibit oscillatory behavior. Introducing the ionophore nigericin restores oscillation in Mdm38p-deficient strains, demonstrating the critical role of K
+/H
+ exchange in sustaining glycolysis.
Potassium contributes to intracellular pH regulation and enzymatic activity in glycolysis, Reduced extracellular K
+ levels decrease the amplitude of oscillations, confirming its importance in regulation.
See also
*
Electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
*
Glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...
*
Potassium ion channel
References
{{Reflist
Control theory
Biochemical reactions