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**13** 

*USA* 

**Reactive Nitrogen Species in** 

María Clara Franco and Alvaro G. Estévez

*Burnett School of Biomedical Sciences, College of Medicine,* 

Nitric oxide is a cellular messenger produced by different cell types in an organism, both in physiological and pathological conditions (Snyder 1993; Beckman and Koppenol 1996; Beckman and Koppenol 1996; Beckman 1996; Colasanti and Suzuki 2000; Pacher, Beckman, and Liaudet 2007). Nitric oxide was first described in biology as the endothelium-derived relaxation factor for its effects on vasodilatation (Ignarro 1990), but soon become evident it have other important physiological functions such as a retrograde messenger in the nervous systems, and during the immune response (Moncada, Palmer, and Higgins 1991). Nitric oxide can also regulate mitochondria respiration (Carreras and Poderoso 2007; Ramachandran et al. 2002), and reacts with oxygen and reactive oxygen species to form reactive nitrogen species, which in turn can damage the cells. The reactivity of nitric oxide and the metabolic state of the cell or tissue are determining factors on the specific actions mediated by nitric oxide. It is not our intention to examine the biochemistry and physiology of nitric oxide, which has been cover in several excellent reviews (Beckman and Crow 1993; Beckman 1996; Pacher, Beckman, and Liaudet 2007), but to concentrate in those nitric oxidederivate species relevant to the regulation of motor neuron apoptosis. However, some relevant aspects of the biochemistry of nitric oxide will be reviewed as the necessary

background to understand the biology of reactive nitrogen species in motor neurons.

One important reaction of nitric oxide is with superoxide (another free radical) to produce the strong oxidant peroxynitrite (Beckman et al. 1990). The importance of this reaction is highlighted by its diffusion-limited rate (between 6.7x109 and 2x1010 M-1s-1)(Padmaja and Huie 1993; Nauser and Koppenol 2002), meaning that every collision of a molecule of nitric oxide with a molecule of superoxide results in the formation of peroxynitrite (Fig 1). In other words, peroxynitrite will be formed when superoxide and nitric oxide are formed simultaneously. The reason peroxynitrite is not formed in large amounts in normal metabolic conditions is the high intracellular concentration of the enzyme superoxide dismutase (SOD)(Rae et al. 1999), which competes for the superoxide with a rate of 2x109 M-1s-1 (Pacher, Beckman, and Liaudet 2007) (Fig 1). Briefly, when the concentration of nitric oxide is 5 times lower than the concentration of SOD, approximately 50% of the superoxide

**1. Introduction** 

**2. Peroxynitrite** 

**Motor Neuron Apoptosis** 

*University of Central Florida, Orlando,* 

Yim, M.B.; Kang, J.H.; Yim, H.S.; Kwak, H.S.; Chock, P.B. & Stadtman, E.R. (1996). A gain-offunction of an amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutant: an enhancement of free radical formation due to a decrease in Km for hydrogen peroxide. *Proceedings of the National Academy of Sciences of the United States of America,* Vol.93, No.12, pp. 5709–5714
