A number of enzymes use an amino acid free radical cofactor. Tyrosyl and tr
yptophanyl radicals react with nitric oxide (NO) with an almost diffusion-l
imited rate. The catalytically competent tyrosyl radical in ribonucleotide
reductase (RR) and prostaglandin H synthase (PGHS) recombines with NO in a
radical-radical reaction. The unstable adduct formed can dissociate to rege
nerate the tyrosyl radical. However, upon prolonged incubation with NO, the
diiron center of mouse RR leaks out, while the adduct is sucessively oxidi
zed into an iminoxyl radical and a nitrotyrosine in PGHS. These data provid
e a plausible mechanism for the physiological inactivation of RR observed i
n various models, and may help in understanding the inhibition of PGHS repo
rted in some cases. Reversible combination with NO is an intrinsic property
of tyrosyl radicals, which also occurs with Y-D(.) and Y-Z(.) in photosyst
em II, where NO has been useful in the analysis of the oxygen-evolving comp
lex.