Quinone methide as a new intermediate in eumelanin biosynthesis.
The conversion of dopachrome to dihydroxyindole(s), a key reaction in eumelanin biosynthetic pathway, has been shown to be under the control of dopachrome conversion factor. Dopachrome conversion factor isolated from the hemolymph of Manduca sexta larvae, which is devoid of any tyrosinase activity, exhibits a narrow substrate specificity and readily bleaches the iminochromes derived from the oxidation of L-dopa, L-dopa methyl ester, and alpha-methyl-L-dopa, but failed to attack the corresponding D-isomers. The product formed in the case of L-dopachrome was identified to be 5,6-dihydroxyindole. Therefore, aromatization of dopachrome seems to accompany its decarboxylation as well. However, the enzyme also converts L-dopachrome methyl ester to an indole derivative indicating that it can deprotonate the alpha-hydrogen when the carboxyl group is blocked. These results are accounted for by the transient formation and further transformation of a reactive quinone methide intermediate during the dopachrome conversion factor-catalyzed reaction. The fact that the enzyme-catalyzed conversion of alpha-methyl dopachrome methyl ester (where both decarboxylation and deprotonation are blocked) resulted in the generation of a stable quinone methide in the reaction mixture confirms this contention and supports our recent proposal that quinone methide and not indolenine is the key transient intermediate in the conversion of dopachrome to dihydroxyindole observed during melanogenesis.
Sugumaran
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Department of Biology, University of Massachusetts, Boston 02125.
Semensi
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D000818:Animals; D002851:Chromatography, High Pressure Liquid; D045563:Indolequinones; D007211:Indoles / Q000737:chemistry*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000737:chemistry; D008543:Melanins / Q000096:biosynthesis*; D009036:Moths / Q000378:metabolism*; D011809:Quinones / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity
D045563:Indolequinones; D007211:Indoles; D008543:Melanins; D011809:Quinones; C041877:eumelanin; C068040:quinone methide; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase