Interaction of melanin with proteins - The importance of an acidic intramelanosomal pH

Melanin is a highly irregular heteropolymer consisting of monomeric units d erived from the enzymatic oxidation of the amino acid tyrosine, The process of melanin formation takes place in specialized acidic organelles (melanos omes) in melanocytes. The process of melanin polymerization requires an alk aline pH in vitro, and therefore, the purpose of an acidic environment in v ivo remains a mystery. It is known that melanin is always bound to protein in vivo. It is also seen that polymerization in vitro at an acidic pH neces sarily requires the presence of proteins. The effect of various model prote ins on melanin synthesis and their interaction with melanin was studied. It was seen that many proteins could increase melanin synthesis at an acidic pH, and that different proteins resulted in the formation of different stat es of melanin, i,e,, a precipitate or a soluble, protein-bound form. We als o present evidence to show that soluble protein-bound melanin is present in vivo (in B16 cells as well as in B16 melanoma tissue). An acidic pH appear ed to be necessary to ensure the formation of a uniform, very high molecula r weight melano-protein complex. The interaction between melanin and protei ns appears to be largely charge-dependent as evidenced by zeta potential me asurements, and this interaction is also increased in an acidic pH, Thus, i t appears that an acidic intramelanosomal pH is essential to ensure maximum interaction between protein and melanin, and also to ensure that all the m elanin formed is protein-bound.