L-Cysteinol

Of the antioxidant/prooxidant mechanisms mediating the regulation of inflammatory mediators, particularly cytokines, oxidative stress-related pathways remain a cornerstone. It is conspicuous that there is a strong association between free radical accumulation (ROS/RNS; oxidative stress) and the evolution of inflammation and inflammatory-related responses. The scenario that upholds a consensus on the aforementioned is still evolving to unravel, from an immunologic perspective, the molecular mechanisms associated with ROS/RNS-dependent inflammation. Cytokines are keynote players when it comes to defining an intimate relationship among reduction-oxidation (redox) signals, oxidative stress and inflammation. How close we are to identifying the molecular basis of this intricate association should be weighed against the involvement of specific signaling molecules and, potentially, transcription factors. L-gamma-Glutamyl-L-cysteinyl-glycine, or glutathione (GSH), an antioxidant thiol, has shaped, and still is refining, the face of oxidative signaling in terms of regulating the milieu of inflammatory mediators, ostensibly via the modulation (expression/repression) of oxygen- and redox-responsive transcription factors, hence termed redox(y)-sensitive cofactors. When it comes to the arena of oxygen sensing, oxidative stress and inflammation, nuclear factor-kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha) are key players that determine antioxidant/prooxidant responses with oxidative challenge. It is the theme therein to underlie current understanding of the molecular association hanging between oxidative stress and the evolution of inflammation, walked through an elaborate discussion on the role of transcription factors and cofactors. Would that classify glutathione and other redox signaling cofactors as potential anti-inflammatory molecules emphatically remains of particular interest, especially in the light of identifying upstream and downstream molecular pathways for conceiving therapeutic, alleviating strategy for oxidant-mediated, inflammatory-related disease conditions.

The δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine (ACV) tripeptide is the first dedicated intermediate in the biosynthetic pathway leading to the penicillin and cephalosporin classes of β-lactam natural products in bacteria and fungi. It is synthesized nonribosomally by the ACV synthetase (ACVS) enzyme, which has been purified and partially characterized from many sources. Due to its large size and instability, many details regarding the reaction mechanism of ACVS are still not fully understood. In this review we discuss the chronology and associated methodology that led to the discovery of ACVS, some of the main findings regarding its activities, and some recent/current studies being conducted on the enzyme. In addition, we conclude with perspectives on what can be done to increase our understating of this very important protein in the future.