The globin superfamily: functions in nitric oxide formation and decay

Abstract

Globin proteins are ubiquitous in living organisms and carry out a variety of functions related to the ability of their prosthetic heme group to bind gaseous ligands, such as oxygen, nitric oxide (NO), and CO. Moreover, they catalyze important reactions with nitrogen oxide species, such as NO dioxygenation and nitrite reduction. The formation of NO from nitrite is a reaction catalyzed by globins that has received increasing attention due to its potential as a hypoxic NO signaling mechanism. In this review, we revisit the current knowledge about the role of globins in NO formation and its physiological implications.

Figure 1

NO generation and NO denitrosylation pathways are regulated by environmental oxygen and globin oxygen binding affinity. The ferric heme can be reduced back to the initial ferrous form by other proteins or reducing agents, allowing for catalytic NO production or scavenging. In six coordinate globins, availability of the ferrous heme form is determined by the binding of the distal histidine side-chain.