Nuclear spin selectivity in enzymatic catalysis: A caution for applied biophysics

Arch Biochem Biophys. 2019 May 30:667:30-35. doi: 10.1016/j.abb.2019.04.005. Epub 2019 Apr 25.

Abstract

Nuclear magnetic ions 25Mg2+, 43Ca2+, and 67Zn2+ suppress DNA synthesis by 3-5 times with respect to ions with nonmagnetic nuclei. This observation unambiguously evidences that the DNA synthesis occurs by radical pair mechanism, which is well known in chemistry and implies pairwise generation of radicals by electron transfer between reaction partners. This mechanism coexists with generally accepted nucleophilic one; it is switched on, when at least two ions enter into the catalytic site. It is induced by both sorts of ions, magnetic and nonmagnetic but it functions by 3-5 times more efficiently with magnetic ions stimulating radical pair mechanism. Decreasing catalytic activity of polymerases by 3-5 times, nuclear magnetic ions 25Mg2+, 43Ca2+, and 67Zn2+ even more strongly, by 30-50 times, increase mortality of cancer cells. The two reasons of this unique phenomenon are suggested: first, the high concentration of nuclear magnetic ions delivered by specific nano-container into the cancer cells, and, second, generation of short DNA fragments by polymerases loaded with nuclear magnetic ions, which is known to activate protein p53, efficiently stimulating apoptosis of cancer cells.

Keywords: Anti-cancer effects; Cancer; DNA synthesis; Isotopes; Magnetic isotope effect.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Biocatalysis
  • Biophysical Phenomena
  • Calcium / administration & dosage
  • Calcium / metabolism
  • DNA / biosynthesis
  • DNA Polymerase beta / chemistry
  • DNA Polymerase beta / metabolism
  • Drug Carriers
  • Electron Transport
  • Enzymes / chemistry*
  • Enzymes / metabolism*
  • Humans
  • Magnesium / administration & dosage
  • Magnesium / metabolism
  • Magnetic Resonance Spectroscopy
  • Magnetics
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Zinc / administration & dosage
  • Zinc / metabolism

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Enzymes
  • DNA
  • DNA Polymerase beta
  • Magnesium
  • Zinc
  • Calcium