TYROSINE-HYDROXYLASE - MECHANISMS OF OXYGEN RADICAL FORMATION

A new mechanism of oxygen radical formation in dopaminergic neurons is proposed, based on the oxidative mechanism of tyrosine hydroxylase. T he cofactor (6R,6S)-5,6,7,8-tetrahydrobiopterin can rearrange in solut ion which allows an autoxidation reaction producing O-2(.-), H2O2 and HO .. The combination of tyrosine hydroxylase and the cofactor produce s more oxygen radicals than does the autoxidation of the cofactor. Thi s production of oxygen radicals could be damaging to dopaminergic neur ons. In the presence of tyrosine, the enzyme produces less radicals th an it does in the absence of tyrosine. Mechanisms are proposed for the generation of reactive oxygen species during the autoxidation of the cofactor and during enzymatic catalysis. The generation, by tyrosine h ydroxylase, of very small amounts of oxygen radicals over the period o f 65 years could contribute to the oxidative stress that causes Parkin son's disease.