Interaction of melanin with proteins--the importance of an acidic intramelanosomal pH.
Melanin is a highly irregular heteropolymer consisting of monomeric units derived from the enzymatic oxidation of the amino acid tyrosine. The process of melanin formation takes place in specialized acidic organelles (melanosomes) in melanocytes. The process of melanin polymerization requires an alkaline pH in vitro, and therefore, the purpose of an acidic environment in vivo 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 necessarily requires the presence of proteins. The effect of various model proteins 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 states of melanin, i.e., a precipitate or a soluble, protein-bound form. We also 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 appeared to be necessary to ensure the formation of a uniform, very high molecular weight melano-protein complex. The interaction between melanin and proteins appears to be largely charge-dependent as evidenced by zeta potential measurements, and this interaction is also increased in an acidic pH. Thus, it appears that an acidic intramelanosomal pH is essential to ensure maximum interaction between protein and melanin, and also to ensure that all the melanin formed is protein-bound.
Mani
I
I
Dept of Cell Biology, Unilever Research Laboratory, Whitefield, Bangalore, India.
Sharma
V
V
Tamboli
I
I
Raman
G
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D020460:Melanosomes / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014466:Ultraviolet Rays
D007477:Ions; D008543:Melanins; D012710:Serum Albumin, Bovine