Enzymes Magnesium-dependent

Cowan, J.A. (2002) Structural and catalytic chemistry of magnesium-dependent enzymes, BioMetals, 15, 225-235. 

Peeraer, Y., Rabijns, A., Collet, J.-F., Van Scafdngen, E. and De Ranter, C. (2004) How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase, Eur. J. Biochem., 271, 3421-3427. 

Many proteins, including many enzymes, contain hghtly bound metal ions. These may be inhmately involved in enzyme catalysis or may serve a purely structural role. The most common tightly bound metal ions found in metalloproteins include copper (Cu+ and Cu +), zinc (Zn +), iron (Fe + and Fe +), and manganese (Mn +). Other proteins may contain weakly bound metal ions that generally serve as modulators of enzyme activity. These include sodium (Na+), potassium (K+), calcium (Ca +), and magnesium (Mg +). There are also exotic cases for which enzymes may depend on nickel, selenium, molybdenum, or silicon for activity. These account for the very small requirements for these metals in the human diet. 

This magnesium-dependent enzyme [EC 1.14.99.19], also known as alkylacylglycerophosphoethanolamine... 

This magnesium-dependent enzyme [EC 2.7.9.3], also known as selenide,water dikinase and selenium donor protein, catalyzes the reaction of ATP with selenide and water to produce AMP, selenophosphate, and orthophosphate. 

FIGURE 24. General mode of action of magnesium-dependent metabolic enzymes. Reproduced [ 2002 Kluwer Academic Publishers] by permission of Springer Science and Business Media from Reference 6... 

In binding experiments, the affinity of magnesium ADP to native membranes and to the isolated calcium dependent ATPase was found to be considerably lower than that of magnesium ATP173. On the other hand, from the inhibition of the calcium-dependent ATPase or the activation of calcium release and ATP synthesis apparent affinities for ADP are obtained that are very similar to those of ATP (Fig. 12). The affinity of ADP for the enzyme apparently depends on its functional state. The affinity of ADP for the membranes under conditions of calcium release depends markedly on the pH of the medium. When the medium pH is reduced from 7.0 to 6.0, the affinity drops by a factor of 10. At pH 7.0 the affinity of the membrane for ADP corresponds to the affinity for ATP to the high affinity binding sites in the forward running mode of the pump. In contrast to the complex dependence of the forward reaction on the concentration of ATP, the dependence of the reverse reaction on ADP seems to follow simple Michaelis-Menten kinetics. 

Over 300 enzymes are dependent upon Mg2+, the largest single group being the phosphotransferases, for which MgATP complex may be regarded as the substrate.q Magnesium has a special role in photosynthesis as a component of chlorophyll. 

Black CB, Cowan JA. 1997. Inert chromium and cobalt complexes as probes of magnesium-dependent enzymes. Evaluation of the mechanistic role of the essential metal cofactor in Escherichia coli exonuclease III. Eur J Biochem 243 684-689. 

Despite these extensive investigations into the interactions of lithium with intracellular enzymes, it is now suggested that concentrations of lithium sufficient to inhibit many magnesium-dependent enzymes may not be achieved within the cell (90). Extracellular actions of lithium therefore must be considered. Other enzyme systems function outside cells, for instance those of the calcium-dependent blood coagulation cascade. These may be affected by lithium, though possibly this may not be relevant to its clinical effects. 

It is possible that the predominant regulatory and recognition role of metals may be at or near the cell surface. For example, two important magnesium-dependent enzymes are adenylate cyclase and phosphodiesterase, which, respectively, synthesise and break down cyclic 3,5-AMP. Intracellular concentrations of this second messenger are known to be reduced by lithium treatment (91, 92). 

Lithium selectively interferes with the inositol lipid cycle (100) and this is the basis for a proposal of a unifying hypothesis for lithium actions (96). Administration of lithium to rats (10 mmol/kg) resulted in a reduction in brain myoinositol and an increase in the reaction substrate inositol-l-phosphate (101). The magnesium-dependent enzyme inositol monophosphate phosphatase, which catalyzes the conversion of inositol monophosphates to inositol, was totally inhibited in rat mammary gland by high concentrations of lithium (250 mM) and partially inhibited by lower concentrations (2 mAf) (102). At clinically relevant concentrations lithium has been shown to inhibit inositol monophosphate phosphatase in bovine brain (K, = 0.8 mM) by substi-... 

Geisler a and Mork A (1990) The interaction of lithium with magnesium-dependent enzymes. In ... 

C. therm, polymerase isolated from Carboxydothermus hydrogenoformans is a magnesium-dependent enzyme with both reverse transcriptase and DNA polymerase activities. C. therm, polymerase has a short half-life at 95 °C and Taq polymerase can be added to the reaction to improve the amplification. 

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