Nitric oxide: a radical molecule in quest of free radicals in proteins

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.