Spontaneous redox reactions of dopaquinone and the balance between the eumelanic and phaeomelanic pathways.

Eumelanogenesis and phaeomelanogenesis diverge at an early stage in pigment formation, namely at the point where dopaquinone, the initial product of tyrosine oxidation by tyrosinase, undergoes one of two types of reaction: either (1) a reductive endocyclisation in which a Michael addition of the side-chain amino group takes place; or (2) a reductive addition of cysteine to give cysteinyldopa. In the former case, the product cyclodopa, is known rapidly to undergo a redox exchange reaction with dopaquinone to yield dopachrome, the precursor of the eumelanogenic pathway. In the second instance, cysteinyldopa is regarded as leading to the formation of benzothiazoles, which are characteristic of phaeomelanin. The precursor molecule of the phaeomelanic pathway is cysteinyldopaquinone. We have examined quantitatively the role of dopaquinone in the non-enzymatic oxidation of 5-S-cysteinyldopa using pulse radiolysis and have demonstrated that the redox exchange reaction between dopaquinone and 5-S-cysteinyldopa occurs spontaneously with a rate constant of 8.8 x 10(5) M(-1) sec(-1). This study has also enabled an improved estimate of < or = 4 x 10(7) M(-1) sec(-1) to be obtained for the rate constant of the reaction of dopaquinone with cyclodopa. Calculations utilising these figures and estimates of the rate constants for the other reactions in early melanogenesis, demonstrate that, whilst similar pathways are invoked, the phaeomelanic pathway predominates in the presence of cysteine, irrespective of the availability of dopaquinone and thus independently of the rate of tyrosinase-catalysed oxidation. This suggests that the balance between the formation of eumelanin and phaeomelanin is regulated principally by the availability of cysteine at the site of melanogenesis.