S-Nitrosothiols and the Bioregulatory Actions of Nitrogen Oxides Through Reactions with Thiol Groups

  • J. S. Stamler
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 196)

Abstract

Chemists have long been aware of the red color that develops upon treatment of thiols with nitrous acid. Shortly after the turn of the last century, Tasker and Jones (1909) reported on the synthesis of benzene thionitrite, which exhibits a red color. The authors further noted that the compound was highly unstable and rapidly decomposed to (biphenyl) disulfide and nitric oxide (NO) gas. Thermal and photolytic decomposition of thionitrites was later shown to involve homolytic fission, as inferred from these early experiments (Lecher and Siefken 1926; Rao et al. 1967; Josephy et al. 1984). Tasker and Jones (1909) also described the thionitrite (or S-nitrosothiol; RS-NO) formed from ethane-thiol treatment with nitrosyl chloride (NOCI). This compound was shown to be significantly more stable than the corresponding benzene thiol derivative, but also disappeared with evolution of nitric oxide. Thus, the well documented importance of the electron withdrawing effect of the thiyl (RS) group in hastening the homolytic decomposition of RS-NO had been appreciated well over 50 years ago. In 1969, Mirna and Hofman provided additional insight into the physical properties of biological RS-NOs. These studies demonstrated the trend for greater stability of thionitrites at low pH. At the same time, differences in the stability of thionitrites derived from cysteine and glutathione were noted. While S nitroso-cysteine rapidly decomposes through homolytic fission, the S-nitroso adduct of glutathione remains stable over a wide (physiological) pH range (Mirna and Hofmann 1969). Shortly thereafter, Field and colleagues, isolated the highly stable thionitrite derivative of N-acetylpenicillamine (Field et al. 1978). More importantly, this work also demonstrated that disappearance of RS-NO can follow heterolytic pathways, specifically, reactions in which IRS-NO formally transfers NO+ (or NO). Additional reactions, persumed to be heterolytic in mechanism, were subsequently reported by Massey and colleagues (1978) and Oae and coworkers (1978) and supported the growing use of thionitrites in organic synthesis as effective nitrosating agents. The notable stability of protein thionitrites has been appreciated most recently, and heterolytic fission of the S-N bond appears to predominate in many biological systems (Stamler et al. 1992a,b,c; Lipton et al. 1993; Stamler 1994).

Keywords

Glutathione Nicotine Disulfide Captopril Clostridium 

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© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • J. S. Stamler
    • 1
  1. 1.Divisions of Respiratory Medicine and Cardiovascular MedicineDuke University Medical CenterDurhamUSA

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