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Download March 21, 1968, Number 12, Page Number 659
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contained in the experimental diet, which presumably interfered with the reabsorption of endogenous magnesium contained in the intestinal secretions.31 BIOCHEMISTRY OFMAGNESIUM Ma gnes ium is an activator in vitro of a host of enzyme systems that are critical to cellular metabolism. Prominent are the enzymes that hydrolyze and transfer phosphate groups, among them the phos-phatases and those concerned in the reactions involving adenosine triphosphate. Since adenosine triphosphate (ATP) is required for glucose utilization, fat, protein, nucleic acid and coenzyme synthesis, muscle contraction, methyl group transfer, sulfate, acetate and formate activation, by inference the activating effect of magnesium extends to all these functions. Additionally, magnesium is required as a cofactor for oxidative phosphorylation in vitro.32"34. Attempts to demonstrate an in vivo counterpart of this requirement in mitochondria obtained from magnesium-deficient animals have led to conflicting results.35"136 Magnesium contributes importantly to macromolecular structure. The highly ordered organization of DNA,37-38 RNA and ribosomes39'40 is stabilized by the presence of this metal. Maximum stabilization of DNA to thermal disruption occurs when a 1:1 stoichiometry is reached between equivalents of magnesium ion and DNA phosphate residues.37 Magnesium is necessary for the structural integrity of ribosomal particles from a variety of sources. The aggregation or dissociation of component particles in ribosomes obtained from Escherichia coli, 39- 41 baker's yeast,42 pea seedlings,43-44 rat liver45 and rabbit reticulocytes46 is critically dependent on the ambient magnesium concentration. Thus, crude extracts ot exponential cultures of E. coli made in 0.01 M Mg+ + predominantly contain a 100S ri-bonucleoprotein. In 0.001 M Mg++ the major ri-bonucleoprotein component has a sedimentation constant of 70S. With 0.0001 M Mg++ ribonucleo-protein particles were present as 30S and SOS peaks only. Additional study showed that each 70S component is made of a 30S and SOS subunit, and that the 100S particle is a dimer of two 70S subunits.3;M1 The f u l l y separated subunits will reaggregate when the magnesium concentration is • increased. The analogous role of magnesium in plant and animal systems cited and the generality ot this phenomenon suggest its fundamental importance in cellular function. Magnesium is further involved in protein synthesis by contributing to -the binding of messenger RNA to the 70S ribosome.47'4* Similar findings were obtained for the interaction ot sRNA with a site on Magnesium is also required for the in vitro synthesis50 and degradation of DNA.51 The metal has also been included in all the amino acid activating 'systems.52'53 The formation of aminoacyl sRNA involves two distinct steps: I. Activation EnzymeEnzyme + Amino Acid + Amino-Acyl-Ade.nylate + PP( ATP II. Transfer Amino Enzyme-Amino-Acyl-Adenylate + Acyl sRNA + Enzyme + AMP. The first step is the amino acid activation step in which a specific amino acyl sRNA synthetase forms a complex with its amino acid in the presence of ATP. This step is known to be magnesium dependent.54-56 Optimal activity of each of the amino acyl RNA synthetases occurs at well defined Mg:ATP ratios.57 In the second step or transfer reaction a specific sRNA accepts its amino acid from the enzyme complex. This step was originally reported not to have a magnesium requirement. 58^" However, if the sRNA has been prepared in a manner likely to remove metals that it naturally contains — for example, dialysis against chelating agents — readdition of magnesium or other divalent cations may become necessary for the transfer reaction. Thus, threonyl sRNA from E. coli, yeast and rat liver ( i l and le u cy l sRNA from yeast62 denatured in this manner show maximal biologic activity for accepting their respective amino acids upon reconstitution with magnesium. The observations point out the more general problem of evaluation of the chemical role of a metal in a biologic system. Direct analysis of endogenous magnesium as well as other divalent metals in such systems is rarely undertaken. Thus, whereas the role of magnesium appears critical, the information necessary to evaluate its specificity in a decisive way is usually not available. Nevertheless, as the most abundant divalent intracellular cation. analogous in vivo function is implied as the most tenable hypothesis. In this regard it is important to point out some recent observations on the interrelations of the major biologic cations.63 It is well known that potassium is generally found to be present in high concentration within cells whereas the intracellular sodium content is low. These ratios are inverted in extracellular fluids. A similar relation between the intracellular and extracellular concentrations ot magnesium and calcium exists. As shown by Figure 1, the intracellular ratios log [K+]/[Na+] and log [Mg+ + ]/[Ca+ + ] are related. In erythrocytes there is a direct relation between K+/Na+ and M g + + / C a + + and an inverse relation between K+/Mg++ and Na+/Ca++.