Magnesium and Manganese Enzymes

In tailoring a shape to fit the substrate, the protein chain is frequently not adaptable enough, and the enzyme makes use of other substances to complete the pattern. Metal ions are amongst the most frequently used, particularly the ions of magnesium and manganese, both of which contain two positive charges and can thus provide a useful link between protein chain and... 

In vitro, cobalt(II) may replace zinc, magnesium, and manganese in a variety of enzymes, without affecting enzymatic activity (Lindskog 1970) this effect is due to the similar ionic sizes of these cations. Whether similar displacement reactions also occur in vivo is not known. Inhaled cobalt particles are rapidly cleared from the lung and excreted. 

Muscle phosphorylase exists in (a) and (b) forms. The latter is half the molecular weight of the former and requires AMP as an activator, but since the AMP concentration (5 x 10 m per liter) required for the activation is not reached in muscle, the (b) form is practically inactive. In passing from one form to another, two enzymes are involved—a proteolytic enzyme catalyzes the breakdown of phosphorylase (a), and another catalyzes the formation of (a) from (b) in the presence of ATP, magnesium, and manganese. The stoichiometry of the second reaction has been studied four molecules of ATP for each molecule of phosphorylase (b) appear to be involved. It has been shown that both phosphorylase (a) and (b) contain pyridoxal phosphate the (b) form contains two such molecules, and the (a) form contains four. The role of the coenzyme in the mechanism of action of phosphorylase is unknown, but the enzyme loses its activity when the coenzyme is dissociated from the main protein molecule by ammonium sulfate activity is restored by the addition of pyridoxal phosphate. 

In this case RNA is synthesized only in the presence of all four ribonucleoside triphosphates, magnesium and manganese ions, and the enzyme RNA polymerase (sometimes called DNA-dependent RNA polymerase, to distinguish it from certain forms of virus-specific RNA polymerase responsible for RNA synthesis in the presence of primer RNA). 

The environment for the phospholipid synthesizing enzymes plays a major role In their activity. By environment I refer to pH, Ion, and membrane lipid requirements. I previously have discussed the pH and Ion requirements. In particular the dichotomy of requirements for magnesium and manganese by the DAG and CDP-DAG pathways of phospholipid synthesis Calcium plays a role In exchange reactionsand has been described as... 

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. 

An ATP-dependent DNase has been partially purified from extracts of E. coli by Oishi (86) and Barbour and Clark (37). It shows an absolute requirement for magnesium or manganese ion and has a broad pH optimum ranging from pH 7.5 to 9.5. The partially purified enzyme preferentially degrades native DNA (including glucosylated T4 DNA) and has an almost absolute requirement for ATP or dATP. Current preparations of the enzyme are also active on denatured DNA however, there is only a slight stimulation of hydrolysis by added ATP. This latter activity may therefore represent some contamination with exonuclease I. The mode of attack is stated to be exonucleolytic. 

In some kinases, such as nucleoside diphosphate kinase, " an intermediate step is the phosphoryl transfer to a group belonging to the enzyme, as happens in ATPase and as was discussed in detail for alkaline phosphatase (Section V.B). In other kinases the phosphoryl transfer occurs directly from the donor to the acceptor in a ternary complex of the enzyme with the two substrates.Often metal ions like magnesium or manganese are needed. These ions interact with the terminal oxygen of the ATP molecule, thus facilitating the nucleophilic attack by the acceptor. The metal ion is often associated with the enzyme. For mechanistic schemes, see the proposed mechanism of action of alkaline phosphatase, especially when a phosphoryl enzyme intermediate is involved. 

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