The early role of nitric oxide in evolution.

Nitric oxide (NO), which today serves many different purposes in regulating complex cellular functions, must have played a crucial role in the early stages of the evolution of life. The formation of NO may have been a critical defence mechanism for primitive microorganisms at a time when life faced the problem of rising atmospheric levels of ozone (03) formed upon photolysis of oxygen (Oz), which occurred shortly after the development of respiration in cyanobacteria. The production of NO by organisms would have allowed neutralization of toxic 03 by chemical reaction outside the cell, thus acting as a protective mechanism against oxidative destruction, allowing evolutionary advantage. Later, NO production might have allowed the control of reactive OZ species within cells before the development of specific electron-accepting enzymes. The pathway of NO formation was then consequently developed further to serve other useful functions. Although mammalian cells produce NO from L-arginine, the origin of this ability might have arisen from the essential process of either nitrification or denitrification in prokaryotic cells.