BIOCHEMISTRY OF MELANIN FORMATION

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Abstract
In this review an endeavor has been made to describe the biochemical mechanisms of melanin formation and to correlate the enzymatic processes involved therein with exptl. and clinical observations on melanin pigmentation. The enzyme tyrosinase, a copper-protein complex, catalyzes the oxidation of tyrosine to dopa and the oxidation of dopa to melanin. Tyrosinase is widely distributed in nature and can be found in plant, insect, marine animal and mammalian tissues. In all these spp. it plays an important role in melanin pigmentation. Until recently it was believed that mammalian tissue contained, instead of tyrosinase, an enzyme called "dopa-oxidase," which supposedly catalyzes only the oxidation of dopa to melanin. It is now known that the original distinction between tyrosinase and dopa-oxidase is not valid. Hence, it is suggested that the single term tyrosinase should be used instead of the separate terms tyrosinase and dopa-oxidase. While tyrosinase obtained from different spp. has some unique properties depending on the particular source, 3 characteristics are common to tyrosinase, under proper conditions, regardless of its origin: (1) the oxidation of tyrosine to melanin is catalyzed by tyrosinase; (2) the tyrosine-tyrosinase reaction is catalyzed by some o-dihydroxyphenyl compound, for example, dopa; (3) the activity of the enzyme is associated with copper ions. Current investigations indicate that tyrosinase is a single enzyme, although unequivocal proof of this is lacking. The prepn. and properties of tyrosinase are discussed. Various substances inhibit melanin formation in vitro and in vivo. The mechanism of the inhibition depends on the particular step,which is blocked,of the tyrosinase-catalyzed series of reactions by which tyrosine is converted to dopa, and eventually to melanin. Melanin-pigmentation in mammals is regulated by biochemical factors, some of which are well defined, such as the concns. of enzyme, substrate, H-ions, sulfhydryl groups, etc. Some of these factors, as well as others which are as yet unknown, are influenced by nutritional, hormonal and neurogenic control. The biochemical basis for melanin pigmentation in several clinical conditions is presented.
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