Is Mg2+ sensed by adenylate kinase and serving as a signal of energy status in biological systems? (a hypothesis)

The contents of adenylates and free magnesium (Mg 2+ ) are controlled by adenylate kinase (AK), which equilibrates specific Mg-bound and free adenylates. Taking into account the true substrates of AK, the reaction is described as: MgATP+AMP free ↔ MgADP+ADP free , and its equilibrium constant ( K ) does not depend on [Mg 2+ ]. However, when the reaction is described in terms of total contents of adenylates, i.e., ATP tot + AMP tot ↔ 2 ADP tot , its apparent K ( K app ) varies from 0.3 to 1.5, depending on [Mg 2+ ]. Here, we argue that Mg 2+ is sensed by AK via the availability of its apparent substrates (total adenylates), and that changes in its K app affect internal [Mg 2+ ]; the higher the K app (and energy status), the lower the [Mg 2+ ], and vice versa. In this way, Mg 2+ becomes a signal of true cellular energy charge. The Mg 2+ -signal controls myriad metabolic and developmental processes, including kinase reactions, photosynthesis, respiration, circadian rhythms, etc., integrating metabolism and development. The AK sensing of Mg 2+ and its control over the Mg 2+ -signal may represent a robust and sensitive measure of energy charge. It may also be universal for any organism containing AK, with shifts in [Mg 2+ ] as vital outputs of its activity and subsequent adenylate metabolism.