The association of zinc and other metals with melanin and a melanin-protein complex

Abstract

two last-mentioned papers it was shown that zinc and a number of other metals occurred in nondialysable form in melanin-protein fractions from the eyes of cattle and perch. The accumulation in these fractions was sufficient to account for most of the zinc in the pigmented tissues.The present work attempts to throw light on the combination between metallic ions and melanin or melanin-protein complexes. The interactions of zinc and other metals with various systems which transform tyrosine or 3:4-dihydroxyphenyl-Lalanine (dopa) to melanin have been studied. Arnow (1938a) showed that a pigment could be obtained by bubbling atmospheric oxygen through an alkaline solution of dopa. Raper (1927) showed that dopa is an intermediate product in the oxidation of tyrosine to melanin by tyrosinase. It is probable that most animal melanins are synthesized by this series of reactions. As the absorption spectrum of the pigment produced by the oxidation of dopa resembles that of natural melanins (Arnow, 1938b) the structures are probably analogous, if not identical. The artificial pigment is therefore suitable for investigating the combination between metals and melanin in the absence of protein.Winternitz (1918) showed that an extract of pig uveal tract catalysed the darkening of tyrosine suspensions, and Calkins (cited by Lerner & Fitzpatrick, 1950) reported the presence of tyrosinase and dopa-oxidase in ox ciliary bodies. It was therefore decided to try to extract from cattle irises and ciliary bodies an enzyme system catalysing the oxidation of tyrosine to melanin, and to use this system to study, in vitro, the effect of metals on melanin formed from tyrosine in the presence of protein. MATERIALS AND METHODSReagents and apparatus. Reagents of A.R. grade were used whenever possible. All aqueous solutions were prepared with twice-distilled water, the final distillation being from, and into, Pyrex-glass vessels. All glass vessels were washed first with 50 % (v/v) HNO3, then with twice-distilled water, and dried in a stainless-steel oven. Subsequently they were scrubbed or rinsed in hot tap water, and then rinsed with twice-distilled water and dried.Preparation of dopa-melanin solution. An aqueous solution of dopa (approx. 0-01 %) was allowed to oxidize in air for several months. The resulting solution was diluted to approximately the original volume. On evaporating 10 ml.of the diluted solution at 500, a dry residue (8-2 mg.) was obtained. The absorption spectrum ofthe solution is given in Fig. 1. The curve corresponds well with that given by Arnow (1938b) for the absorption in the visible region of his dopamelanin. The small peak at 280 m,u. may be due to unchanged dopa (cf. Mason, 1948).

Vitiligo Caused By Chloroquine Phototoxicity

“…The theoretica l mec hani sm of the complex formation is that of chargetransfer complexes (9), further hypotht:s is co ncern in g the pigmentati on di sturbances observed during chlo roquine therapy. is the possible interaction between chloroquine and mctal s s uch as copper (10). The toxic effect 01" chloroquine then wou ld be expla ined by interact ion w ith the cop pe r-requirin g e nzyme tyro[) in ase ( 11 ).…”

Zinc, Cobalt and Selenium Concentrations in the Premature and Full-Term Newborn Eye

“…Human eye tissue levels of barium and zinc have been studied [3]. Much information is available about concentrations of inorganic trace ele ments in fish and animal eyes [4,7,9,10] i.e., fish eye tissue levels of zinc and copper as well as levels of cobalt, copper, manganese, barium and selenium in various mammals. The lowest levels ofZn were observed in the eye lens and the highest ones in the choroid, retina and iris of fish and mammals in gen eral [7], Zn levels in adult eye tissues are higher than those in other soft body tissues [8], Mawson ancl Fischer [8] determined Zn of soft human body as being about 100 ppm.…”

Comparative Biochemistry of the Phenolase Complex

“…A number of attempts have been made to determine the composition of naturally occurring melanin. The eaily results, which have been summarized by Waelsch (484 ; also see 462,469,472,473,[485][486][487][488][489][490], illustrate the difficulty of separating unchanged melanin from concomitant protein, since the analyses reported are broadly inconsistent. However, three developments arise from this work.…”

“…230,493). It has also been observed that, while zinc does riot combine with melanin formed in vitro and combines only to a small extent wit,h amelanic (phenolase-active) proteins from ocular tissue, it is bound to a considerable extent by melanoprotein formed from these components (487). Furthermore, natural melanins bind heavy metals, becoming darker in the process (486).…”