View - ResearchSpace@Auckland - The University of Auckland

enzyme and are competitively reversed by the normal substrate L-arginine, but not D-
arginine. With prolonged incubation, the inhibitors appear to exhibit non-competitive
properties (Marletta, Tayeh et al. 1990). Ebselen is a selenium containing antioxidant (2 -
phenyl, 2-benzisoselenazol-3-(2h)-one) which is synthetic analog of glutathione peroxidase
and is able to inhibit both iNOS and cNOS (Hibbs, Taintor et al. 1990).
Figure 3.4: The chemical structures of the nitric oxide synthase inhibitors
cooe ,,4,\,*"
cooo
'\r/t'
,,A__^^(.*
lW-Amino-u-arglnlnc
tt'\*lt'
,,4,,\'*" -.A,r"-f'
'.)\".
l-Arglnine
r-NMMA
\ t-NNA
cooo
t€anlvanrnc
The structures of arginine and of the arginine analogues most frequently used as inhibitors of the NO
synthases with the predominant ionic species at neutral pH shown.
Taken from Knowles RG, Moncada S. Nitric oxide synthases in mammals. BiochemicalJournal 1994;
298 (21:249-255 (Knowles and Moncada 1994).
Some NOS inhibitors occur naturally such as aminoguanadine a competitive inhibitor, and
two of the compounds discussed above (L-NMMA and L-NAME) also occur naturally in very
small amounts, and so may also operate as a control at substrate level. Interestingly, the
90