Molecular mechanisms for mammalian melanogenesis

Melanogenesis is an important biochemical process for the production of skin pigments which protect many animals from the damage of solar radiation. The abnormalities in melanogenesis are associated with albinism, vitiligo, as well as malignant melanoma in humans. In the lower forms of animals viz., insects, the exoskeleton is hardened to protect their soft bodies by a process called sclerotization, which is often accompanied by melanization. Recent advances in the biochemistry of sclerotization and melanization reveal remarkable similarity between these two processes. The seven stages of sclerotization are: (a) enzymatic oxidation of N ‐acyldopamine, (b) Michael‐1,4‐addition reactions of N ‐acyldopamine quinone, (c) tautomerization of quinone to quinone methide, (d) Michael‐1,6‐addition of quinone methides, (e) tautomerization of N ‐acyldopamine quinone methide to 1,2‐dehydro‐ N ‐acyldopamine, (f) enzymatic oxidation of 1,2‐dehydro‐ N ‐acyldopamine, and (g) the reactions of resultant quinonoid compounds. Amazingly, striking similarities in the reaction sequences are found in the melanization process starting from dopa. These comparisons predict a central role for quinone methides as reactive intermediates during melanization. Accordingly, recent studies provide increasing evidence in favor of this proposition.