Nitric oxide biological half-life

Destruction of nitric oxide by superoxide in the buffers is more likely to account for the short half-life of nitric oxide in vitro. Superoxide dismutase (15-100 U/ml) substantially increased the apparent half-life of EDRF, strongly suggesting that superoxide contributes to the short biological half-life of nitric oxide. In the perfusion cascade bioassay system, the buffers are bubbled with 95% oxygen, contain 11 mM glucose as well as trace iron plus copper contamination and are incubated under the weak ultraviolet (UV) radiation of fluorescent lights. These are prime conditions for the autoxidation of glucose to form small amounts of superoxide in sufficient amounts to account for the short half-life of nitric oxide in nanomolar concentrations. The rate of reaction between superoxide and nitric oxide is 6.7 X 10 M sec L The shortest half-life of nitric oxide measured is approximately 6 sec. To achieve a half-life of 6 sec, the steady state concentration of superoxide would only need to be 17 pM, calculated as ln(2)/ (6 sec X 6.7 X 10 M" sec )-... 

Regardless of the exact reaction mechanism, these results suggest that the biological half-life of nitric oxide per se would be shortened by ONOO". On the other hand, if the net effect of the ONOO"/nitric oxide reaction was to increase the yield of nitrosothiol, it is conceivable that the biological effects of nitric oxide could be prolonged. 

Most messenger molecules encode information within their shape, which is recognized by a specific receptor. Nitric oxide is the smallest of biological messenger molecules, with the possible exception of carbon monoxide. Because of its chemical simplicity, nitric oxide must convey information by its concentration, which is interpretable by the spatial proximity of the source and target cells and the short duration of nitric oxide. Thus, the short half-life and limited diffusion distance of nitric oxide confers specificity, allowing the target tissue to derive information based solely on nitric oxide concentration. 

Clearly, the short half-life of nitric oxide is an important determinant for its biological function, but the chemical basis for this short half-life is still unknown. It cannot be due to the most commonly accepted mechanism reaction with oxygen to form nitrogen dioxide. 

Rate of biological inactivation of nitric oxide. The apparent first-order rate constants were calculated as the natural logarithm of two divided by the half-life of nitric oxide measured in perfusion cascades. The half-lives were 30 sec with room air and 6-8 sec with 95% oxygen (Furchgott and Vanhoutte, 1989). Under anaerobic conditions, nitric oxide is indefinitely stable. The slope of the line give a second-order rate constant for the inactivation of nitric oxide by oxygen as approximately 100 M" sec". ... 

Comparison of the observed pseudo-first-order decay of biological activity with a half-life of 30 sec at normal oxygen tensions versus decomposition via nitrogen dioxide by pseudo-second-order kinetics predicted by Reaction 4. The loss of nitric oxide through formation of nitrogen oxide is twice as fast as calculated by Reaction 4 because each nitrogen dioxide formed rapidly attacks a second nitric oxide to form nitrite. 

Beckman, J. S., and Koppenol, W. H. (1992). Why is the half-life of nitric oxide so short Biology of Nitric Oxide. 2. Enzymology, Biochemistry and Immunology. Portland Press Proceedings, London. 

If CN is indeed a neuromodulator, it contrasts with nitric oxide. Except for conversion to thiocyanate by sulfurtransferase enzymes, CN is relatively stable in biological systems and exists to the extent of about 3 pM in human blood. Those who smoke have elevated blood CN levels. Nitric oxide, on the other hand, spontaneously breaks down in biological fluids, having a half-life of a few seconds. Thus CN can accumulate in biological materials, collecting in lipoid depots since it is lipid soluble. Cyanide also forms complexes with albumin through addition to disulfide bonds, and one study proposed this interaction to be a mechanism to remove CN from blood. ... 

We examine here a number of reaction pathways for nitric oxide, with the emphasis on assessing their biological relevance. To date, the fastest reaction for nitric oxide with clear toxicological significance is that with superoxide to produce ONOO" (Huie and Padmaja, 1993). Thus, the chemistry and reactivity of ONOO" are discussed at length. In addition, the interaction between ONOO" and nitric oxide is examined with respect to its effects on nitric oxide half-life as well as effects on peroxynitrite reactivity toward phenol. Reaction mechanisms are proposed to account for the nitrated, hydroxylated, and nitrosated phenolic products seen. 

Nitric oxide belongs to the oldest molecules on earth and has been developed in the primitive atmosphere of the cooling planet (Moncada and Martin 1993). Due to its high reactivity with other molecules, its half-life time in biological systems is only... 

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