A site-specific mechanism for free radical induced biological damage: The essential role of redox-active transition metals

Mordechai Chevion*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

479 Scopus citations

Abstract

The metal-mediated site-specific mechanism for free radical-induced biological damage is reviewed. According to this mechanism, cooper- or iron-binding sites on macromolecules serve as centers for repeated production of hydroxyl radicals that are generated via the Fenton reaction. The aberrations induced by superoxide, ascorbate, isouramil, and paraquat are summarized. An illustrative example is the enhancement of double-strand breaks by ascorbate/copper. Prevention of the site-specific free radical damage can be accomplished by using selective chelators for iron and copper, by displacing these redox-active metals with other redox-inactive metals such as zinc, by introducing high concentrations of hydroxyl radicals scavengers and spin trapping agents, and by applying protective enzymes that remove superoxide or hydrogen peroxide. Histidine is a special agent that can intervene in free radical reactions in variety of modes. In biological systems, there are traces of copper and iron that are at high enough levels to catalyze free-radical reactions, and account for such deleterious processes. In the human body Fe/Cu = 80/1 (w/w). Nevertheless, both (free) copper and iron are soluble enough, and the rate constants of their reduced forms with hydrogen peroxide are sufficiently high to suggest that they might be important mediators of free radical toxicity.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalFree Radical Biology and Medicine
Volume5
Issue number1
DOIs
StatePublished - 1988

Keywords

  • Ascorbate
  • Copper
  • DNA
  • Free radicals
  • Histidine
  • Iron
  • Isouramil
  • Site-specific damage
  • Superoxide
  • Zinc

Fingerprint

Dive into the research topics of 'A site-specific mechanism for free radical induced biological damage: The essential role of redox-active transition metals'. Together they form a unique fingerprint.

Cite this