Download March 21, 1968, Number 12, Page Number 659

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Transcript
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++.