The Critical Role of Adenylate Kinase in Regulating the Glycolysis Rate in Cells

TL;DR

This paper explains how adenylate kinase helps regulate glycolysis in cells by linking ATP levels to AMP, which controls the rate of energy production.

Contribution

The study reveals that adenylate kinase enables negative feedback regulation of glycolysis through AMP, which is crucial for stabilizing ATP levels.

Findings

Adenylate kinase converts small ATP changes into large AMP changes, which activates glycolysis via PFK.

Negative feedback regulation of glycolysis is achieved through AMP, not directly through ATP inhibition of PFK.

ATP production via adenylate kinase is minimal, and energy metabolism is regulated by energy charge rather than ATP concentration alone.

Abstract

The role of adenylate kinase in regulating the glycolysis rate and the potential contribution of the adenylate kinase reaction to ATP production were examined using mathematical models of energy metabolism in human erythrocytes and resting anaerobic mammalian skeletal muscle. The adenylate kinase reaction was shown to play a critical role in the regulation of cellular energy metabolism. Through the action of adenylate kinase, small changes in intracellular [ATP] give rise to large changes in [AMP], a potent activator of glycolytic flux via the activation of phosphofructokinase (PFK). This mechanism ensures an increase in the glycolytic rate as [ATP] decreases within the physiological range of ATP concentrations. As a result, negative feedback regulation of glycolysis by [ATP] is established, allowing the rate of ATP production to adjust to the energy demands of the cell and thereby stabilizing [ATP] under varying rates of ATP consumption. Importantly, allosteric inhibition of PFK by ATP alone was insufficient to provide negative feedback regulation of glycolysis via [ATP]. The contribution of the adenylate kinase reaction to ATP production appears to be negligible. Also, due to the presence of adenylate kinase in cells, energy metabolism is regulated not by the absolute concentration of ATP, but by the energy charge or the ratio of [ATP] to the sum of [ATP], [ADP], and [AMP].

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