Chemistry Reference
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hydrated nitric oxide.
120,121
Theoretically and experimentally there is little support for proposed hydrated
nitric oxide steps.
Ab initio
methods predict less than 2 kJ mol
−
1
stabilization for any direct van der
Waals complexes,
115
and there is no spectroscopic or reaction evidence for any such species. For example,
oxygen scrambling in the NO/
18
OH
2
system is not detectable under the conditions for “hydrated nitric
oxide” in these mechanisms. A more likely explanation for these kinetics is the operation of a competitive
dimer/monomer rate law, as has been observed for the addition of secondary amines to nitric oxide.
116
The question of mechanism is of considerable importance in all of nitric oxide's biological, environ-
mental, and atmospheric chemistry, where low concentrations make dimerization pathways very unlikely.
If transient radical intermediates such as ONOO are present, then their chemistry is of considerable impor-
tance. These mechanistic issues remain an active area of research for scientists interested in free radicals
in biology.
122,123
4.8 Biochemical and organic reactions of nitric oxide
Unlike any other development in its chemistry, the recognition of nitric oxide's important roles in biology
has triggered an avalanche of new research.
124 - 126
The initial discoveries
124,127,128
in the early 1980s
were greeted with considerable initial skepticism by the biomedical community.
129
Commonplace opinion
was that, since nitric oxide was a radical, how could it have any lifetime or specificity in a cell? Three
independent lines of research rapidly led to the acceptance and recognition of its biological role. Nitric
oxide's role in understanding nitroglycerine vasodilation
130
was the initial discovery, but equally important
were Hibb's pioneering study into the macrophage requirements for phagolysosome activity,
131 - 133
and
Tannenbaum and Marletta's studies into metabolic levels of nitrite and nitrate.
134,135
All of these studies laid
the foundation for understanding nitric oxide's constitutive and inducible physiological roles. Subsequent
studies helped recognize the biosynthetic source of nitric oxide from the oxygenation of arginine,
136,137
and the normal nondietary basal levels of nitrite and nitrate.
135
It is now recognized that the main nitric
oxide pathway (Figure 4.5 and Equation 4.19), have heme enzymes directly involved in the generation
and sensing of nitric oxide.
NH
2
H
2
N
NH
NH
2
HO
2
C
arginine
2H
2
O
−
,2O
2
,2H
+
−
(4.19)
O
H
2
N
+NO
NH
NH
2
HO
2
C
citrulline
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