NITROSATIVE STRESS - METABOLIC PATHWAY INVOLVING THE FLAVOHEMOGLOBIN

Nitric oxide (NO) biology has focused on the tightly regulated enzymat ic mechanism that transforms L-arginine into a family of molecules, wh ich serve both signaling and defense functions. However, very little i s known of the pathways that metabolize these molecules or turn off th e signals. The paradigm is well exemplified in bacteria where S-nitros othiols (SNO)-compounds identified with antimicrobial activities of NO synthase-elicit responses that mediate bacterial resistance by unknow n mechanisms. Here we show that Escherichia coli possess both constitu tive and inducible elements for SNO metabolism. Constitutive enzyme(s) cleave SNO to NO whereas bacterial hemoglobin, a widely distributed f lavohemoglobin of poorly understood function, is central to the induci ble response. Remarkably, the protein has evolved a novel heme-detoxif ication mechanism for NO. Specifically, the heme serves a dioxygenase function that produces mainly nitrate. These studies thus provide new insights into SNO and NO metabolism and identify enzymes with reaction s that were thought to occur only by chemical means. Our results also emphasize that the reactions of SNO and NO with hemoglobins are evolut ionary conserved, but have been adapted for cell-specific function.