Cysteinyl-dopa

Phaeomelanins — This gronp consists of sulfur-containing polymers composed of benzothiazines, derived from cysteinyl-DOPA. 

Scheme 10.3 illustrates the route that ultimately generates eumelanin. Dopaquinone, 10.7, is converted, via leucodopachrome, 10.8, dopachrome, 10.9, 5,6-dihydroxyindole-2-carbo)ylic acid, 10.10 (DHICA), and 5,6-dihydrojyindole, 10.11 (DHI), into the reactive intermediate indolequinone, 10.12, from which an oxidative polymerisation leads to eumelanin. Scheme 10.4 illustrates the route towards pheomelanin, whereby dopaquinone, 10.7, reacts with the amino acid cysteine, 10.13, to give cysteinyl DOPA derivatives 10.14a/ b, which are converted via intermediates I0.l5a/b and 10.16a/b into dihydrobenzothiazines 10.17a/b. Details beyond this stage are uncertain. 

Ito and G. Prota, A facile one-step synthesis of cysteinyl-dopas using mushroom tyrosinase, Experientia, 33 1118 (1977), and references therein. 

Dopachrome also undergoes a nonenzymatic reaction to form dihidroxyindole (DHI), the precursor of DHI-eumelanins. For the formation of phaeomelanins, dopaquinone is first transformed in cysteinil-DOPA and then in cysteinyl-dopaquinone which suffers a nonenzymatic polymerization. The polymerization of monomers and the association of melanins with proteins is not yet completely elucidated and may involve other intermediates. ... 

Pheomelanins (yellow, red, or brown) that are initially synthesized just like eumelanins, but DOPA undergoes cysteinylation, directly or by the mediation of glutathione, then polymerizes... 

Similar chemical reactions are involved in the reaction of other catechols such as the catecholamines, dopamine, and L-dihydroxyphenylalanine (L-DOPA) with cysteine or GSH [149-152] and can lead to the generation of mitochondrial toxins with relevance to Parkinson s disease [153-155], As well as possible cytotoxic effects of lowering cellular thiol levels or binding to cysteine residues at die active site of specific enzymes, flavonoids could act beneficially by acting to limit the formation of the potentially cytotoxic catecholamine-thiol adducts, in a manner similar to that observed for dihydro-lipoic acid [151], Because of the structural similarity of the flavonoid B-ring and their ability to donate electrons efficiently to form quinones, it is conceivable that specific flavonoids may be of use to prevent such neurotoxic compounds as 5-S-cysteinyl dopamine from forming in vivo. 

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