Magnesium magnetic isotope effect: A key to the mechanochemistry of phosphorylating enzymes as molecular machines

The discovery of the powerful magnesium isotope effect on enzymatic ATP synthesis provides a new insight into the mechanochemistry of enzymes as molecular machines. The catalytic activities of ATPase, creatine kinase, and glycerophsphate kinase containing a Mg²⁺ ion with magnetic isotope nuclei (²⁵Mg) were found to be two to four times higher than those of the enzymes with spinless, nonmagnetic magnesium cation isotopes (²⁴Mg or ²⁶Mg). This demonstrates unambiguously that ATP synthesis is a spin-selective process involving Mg2+ as the electron-accepting reagent. ATP synthesis proceeds in an ion-radical pair consisting of an ADP oxyradical and Mg²⁺. In this process, the magnesium bivalent cation is the key agent that transforms the mechanics of a protein molecule into chemical processes. This ion is the crucial structural component of enzymes as mechanochemical molecular machines.     

Magnetic isotope and magnetic field effects on the DNA synthesis

Magnetic isotope and magnetic field effects on the rate of DNA synthesis catalysed by polymerases β with isotopic ions ²⁴Mg²⁺, ²⁵Mg²⁺ and ²⁶Mg²⁺ in the catalytic sites were detected. No difference in enzymatic activity was found between polymerases β carrying ²⁴Mg²⁺ and ²⁶Mg²⁺ ions with spinless, non-magnetic nuclei ²⁴Mg and ²⁶Mg. However, ²⁵Mg²⁺ ions with magnetic nucleus ²⁵Mg were shown to suppress enzymatic activity by two to three times with respect to the enzymatic activity of polymerases β with ²⁴Mg²⁺ and ²⁶Mg²⁺ ions. Such an isotopic dependence directly indicates that in the DNA synthesis magnetic mass-independent isotope effect functions. Similar effect is exhibited by polymerases β with Zn²⁺ ions carrying magnetic ⁶⁷Zn and non-magnetic ⁶⁴Zn nuclei, respectively. A new, ion–radical mechanism of the DNA synthesis is suggested to explain these effects. Magnetic field dependence of the magnesium-catalysed DNA synthesis is in a perfect agreement with the proposed ion–radical mechanism. It is pointed out that the magnetic isotope and magnetic field effects may be used for medicinal purposes (trans-cranial magnetic treatment of cognitive deceases, cell proliferation, control of the cancer cells, etc).