Magnesium and cell energetics: At the junction of metabolism of adenylate and non-adenylate nucleotides

Free magnesium (Mg2+) represents a powerful signal arising from interconversions of adenylates (ATP, ADP and AMP). This is a consequence of the involvement of adenylate kinase (AK) which equilibrates adenylates and uses defined species of Mg-complexed and Mg-free adenylates in both directions of its reaction. However, cells contain also other reversible Mg2+-dependent enzymes that equilibrate non-adenylate nucleotides (uridylates, cytidy-lates and guanylates), i.e. nucleoside monophosphate kinases (NMPKs) and nucleoside diphosphate kinase (NDPK). Here, we propose that AK activity is tightly coupled to activities of NMPK and NDPK, linking adenylate equilibrium to equilibria of other nucleotides, and with [Mg2+] controlling the ratios of Mg-chelated and Mg-free nucleotides. This coupling establishes main hubs for adenylate-driven equilibration of non-adenylate nucleotides, with [Mg2+] acting as signal arising from all nucleotides rather than adenylates only. Further consequences involve an overall adenylate control of UTP-, GTP-and CTP-dependent pathways and the availability of sub-strates for RNA and DNA synthesis.

Automated summary

Free magnesium ions serve as a powerful signal derived from the interconversion of adenylates. Adenylate kinase (AK) plays a role in equilibrating adenylates and using specific forms of Mg-complexed and Mg-free adenylates. In addition, other reversible Mg2+-dependent enzymes equilibrate non-adenylate nucleotides. AK activity is closely linked to the activities of these enzymes, establishing main hubs for equilibration of non-adenylate nucleotides with Mg2+ controlling the ratios of Mg-chelated and Mg-free nucleotides. This coupling has consequences for various cellular pathways and nucleotide availability for RNA and DNA synthesis.