Perferryl complex of nitric oxide synthase: role in secondary free radical formation

Biochim Biophys Acta. 2002 Jan 15;1569(1-3):111-6. doi: 10.1016/s0304-4165(01)00241-0.

Abstract

Neuronal nitric oxide synthase (NOS I) has been shown to generate nitric oxide (NO*) and superoxide (O(2)*-)during enzymatic cycling, the ratio of each free radical is dependent upon the concentration of L-arginine. Using spin trapping and electron paramagnetic resonance (EPR) spectroscopy, we recently reported that NOS I can oxidize ethanol (EtOH) to alpha-hydroxyethyl radical (CH(3)*CHOH). We speculated that the perferryl complex of NOS, (NOS-[Fe(5+)[double bond]O](3+)) was responsible for the generation of CH(3)*CHOH. Using potassium monopersulfate (KHSO(5)) to oxidize the heme of NOS I to NOS-[Fe(5+)[double bond]O](3+), we were able to demonstrate that this perferryl complex can oxidize L-arginine to L-citrulline and NO*. Even in the absence of L-arginine, EtOH was oxidized to CH(3)*CHOH by NOS-[Fe(5+)[double bond]O](3+). Sodium cyanide (NaCN), a heme blocker, inhibited the formation of CH(3)*CHOH by NOS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arginine / metabolism
  • Binding Sites
  • Carbon Radioisotopes
  • Citrulline / biosynthesis
  • Electron Spin Resonance Spectroscopy
  • Ethanol / chemistry
  • Free Radicals / chemistry
  • Heme / antagonists & inhibitors
  • Heme / chemistry
  • Humans
  • Iron / chemistry
  • NADP
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / isolation & purification
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I
  • Oxidation-Reduction
  • Potassium Compounds
  • Recombinant Proteins / metabolism
  • Sodium Cyanide / pharmacology
  • Spin Trapping
  • Sulfates

Substances

  • Carbon Radioisotopes
  • Free Radicals
  • Potassium Compounds
  • Recombinant Proteins
  • Sulfates
  • perferryl iron
  • Citrulline
  • Ethanol
  • Heme
  • NADP
  • potassium persulfate
  • Arginine
  • Iron
  • NOS1 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Sodium Cyanide