Dopaquinone Conversion and Related Reactions

The biosynthetic pathway of melanin is branched into pheomelanogenesis and eumelanogenesis at the stage of dopaquinone conversion. In the presence of intracellular thiols such as cysteine, dopaquinone binds to the sulfhydryl group of thiols, whereas under lower concentration of thiols dopaquinone spontaneously undergoes intramolecular cyclization through the alanyl side chain. The binding of cysteine produces cysteinyldopa necessary for pheomelanogenesis, whereas the cyclized product, cyclodopa further transforms into eumelanin. In this chapter, we introduce computational studies for cyclization and thiol binding for dopaquinone and structurally similar o-quinones with the emphasis on the competitive behavior between the two reactions. As a result, remarkable charge redistributions were observed during cyclization and thiol binding. From this point of view, the HOMO and LUMO levels of o-quinone are pointed out as important factors affecting the reactivity and the competition between the two reactions. Furthermore, a mechanistic issue of thiol binding is also discussed based on the atomic-scale simulation results, which showed the presence of unusual reaction intermediate. Our approach clarifies branched reactions of dopaquinone and resembling o-quinones from atomic nuclei and electrons world.