Identification of cysteinyldopa-derived units in eumelanins from mammalian eyes.
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Biomedical subjects
Publications and source records attributed to G Prota.
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Evidence for the postulated role of glutathione reductase in melanin pigmentation has been obtained by determinations of the glutathione concentrations in Tortoiseshell guinea pig skin of different colors (black, yellow, red, and white). As expected, the lowest levels of reduced glutathione (GSH) were found associated with eumelanin type pigmentation, whereas the highest ones were found in the skin with phaeomelanin producing melanocytes. On the other hand, white skin of guinea pig having no active melanocytes showed GSH levels which were intermediate between those of the black and yellow areas. These results are consistent with the view that the activity of the enzyme glutathione reductase, though not primarily related to pigmentation, plays an important role in the regulation and control of the biosynthetic activity of melanocytes leading to various types of melanin pigments.
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The color of mammalian hair, skin, and eyes results mainly from the secretory products of melanocytes. These secretory products consist of a wide range of melanin pigments with different structures and compositions. These include black or brown nitrogenous eumelanins; yellow or reddish brown, sulfur-containing pheomelanins, e.g., the trichochromes of low molecular weight; and other pigments whose chemical and physical properties are intermediate between those of typical eumelanins and pheomelanins. Despite the evident differences in molecular size and general properties, all these pigments are biogenetically related, and they arise from a common mmetabolic pathway in which dopaquinone is the key intermediate. The current state of knowledge on the molecular mechanisms governing the etabolic fate of dopaquinone in melanocytes is discussed with special reference to the role of such sulfhydryl compounds as cysteine and glutathione in melanogenesis.
The urine of patients with melanoma metastases and increased urinary excretion of 5-S-cysteinyldopa was examined for trichochromes. Five of 16 patients showed urinary excretion of trichochromes B and C. None excreted trichochromes E or F. All patients showing trichochrome excretion had very large amounts of cysteinyldopa in their urine.
A convenient one-step procedure, based upon the tyrosinase co-oxidation of dopa and cysteine, is reported for the synthesis of 5-S-cysteinyldopa (I) in 74% yield. Secondary products of the reaction turned out to be 2-S-cysteinyldopa (II, 14%), 2,5-S, S-dicysteinyldopa (iv, 5%), and the hitherto unknown 6-S-cysteinyldopa (III, approximately 1%).
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The pigments in melanomas from 2 patients were studied with regard to solubility and chemical composition. Melanoma pigment from a patient with red-blonde hair was alkali-soluble and contained 9 or 10% sulfur and was thus of phaeomelanic type. Melanoma pigment from a patient with red-brown hair was insoluble in 0.2 N NaOH. Its sulfur content was 6%. This pigment was eumelanic with regard to solubility characteristics but the sulfur content was higher than previously observed for eumelanin.
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The interaction of two natural tetra-azacyclopentazulene dyes with native calf thymus DNA was studied by means of microcalorimetric, viscosimetric, and spectroscopic measurements. The results are consistent with the hypothesis of an intercalative-binding. However, comparison of calorimetric studies shows that the changes in enthalpy associated with the interaction of these compounds with DNA are, in absolute value, significantly lower than those found with known intercalating agnets (daunomycin, ethidium bromide). The influence of these dyes on the template capacity of DNA in the in vitro synthesis of nucleic acids was also determined. Under the conditions used, these compounds selectively inhibited DNA synthesis. No appreciable inhibitory effect upon E. coli RNA polymerase was observed. Both compounds had greater inhibitory effect on rat liver high molecular weight DNA polymerase than E. coli DNA polymerase I. Zoanthoxanthin was a more effective inhibitor than 3-norzoanthoxanthin.
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Melanosomes of phyllomedusid frogs are unusually large and are composed of an amorphous matrix of thick fibers. Their hitherto undescribed dark red pigment is neither phaeomelanin nor eumelanin, but seems to be related to melanins. Melanophores of at least one of these species, Agalychnis dacnicolor, exhibit color change in direct response to illumination, and it is suggested that these chromatophores are innervated.
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