Adenylate-driven equilibration of both ribo- and deoxyribonucleotides is under magnesium control: Quantification of the Mg2+-signal

Abstract

Nucleoside mono-, di- and triphosphates (NMP, NDP, and NTP) and their deoxy-counterparts (dNMP, dNDP, dNTP) are involved in energy metabolism and are the building blocks of RNA and DNA, respectively. The production of NTP and dNTP is carried out by several NMP kinases (NMPK) and NDP kinases (NDPK). All NMPKs are fully reversible and use defined Mg-free and Mg-complexed nucleotides in both directions of their reactions, with Mg²⁺ controlling the ratios of Mg-free and Mg-complexed reactants. Their activities are driven by adenylates produced by adenylate kinase which controls the direction of NMPK and NDPK reactions, depending on the energy status of a cell. This enzymatic machinery is localized in the cytosol, mitochondria, and plastids, i.e. compartments with high energy budgets and where (except for cytosol) RNA and DNA synthesis occur. Apparent equilibrium constants of NMPKs, based on total nucleotide contents, are [Mg²⁺]-dependent. This allows for an indirect estimation of internal [Mg²⁺], which constitutes a signal of the energetic status of a given tissue/cell/compartment. Adenylates contribute the most to this Mg²⁺-signal, followed by uridylates, guanylates, and cytidylates, with deoxynucleotides’ contribution deemed negligible. A method to quantify the Mg²⁺-signal, using nucleotide datasets, is discussed.