Peracid oxidation of an N-hydroxyguanidine compound: a chemical model for the oxidation of N omega-hydroxyl-L-arginine by nitric oxide synthase

J Med Chem. 1993 Sep 3;36(18):2666-70. doi: 10.1021/jm00070a010.

Abstract

Arginine is oxidized by a class of enzymes called the nitric oxide synthases (NOS) to generate citrulline and, presumably, nitric oxide (.NO). N-Hydroxylation of a guanidinium nitrogen of arginine to generate N-hydroxyarginine (NOHA) has been shown to be a step in the biosynthesis of .NO. In an effort to elucidate the mechanism by which further oxidation of NOHA occurs, the oxidation of a model N-hydroxyguanidine compound by several peracids was studied in depth. This oxidative chemistry is a possible model for the enzymatic process since the corresponding urea (or citrulline equivalent product) is obtained along with an oxidized nitrogen species. The oxidized nitrogen product was, however, not .NO but rather HNO. .NO generation in this chemical system and in the enzymatic process would require another one-electron oxidation. The mechanistic details of this are further discussed.

Publication types

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

MeSH terms

  • Amidines / chemistry*
  • Amino Acid Oxidoreductases / metabolism*
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Chlorobenzoates / chemistry*
  • Chromatography, Gas
  • Chromatography, High Pressure Liquid
  • Hot Temperature
  • Luminescent Measurements
  • Models, Chemical*
  • Nitric Oxide / chemistry
  • Nitric Oxide Synthase
  • Oxidation-Reduction
  • Piperidines / chemistry*

Substances

  • Amidines
  • Chlorobenzoates
  • Piperidines
  • 3-chlorobenzoic acid
  • N-(N-hydroxyamidino)piperidine
  • Nitric Oxide
  • N(omega)-hydroxyarginine
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases