cysteinyldopa and Albinism

The melanocyte activity was studied by analysis of the urinary excretion of indolic and cysteinyldopa compounds. One eumelanin marker, 5,6-dihydroxy-indole-2-carboxylic acid was identified and quantified in normal urine. However, its low concentration and sensitivity to oxidation made it less suitable for clinical studies. A methylated derivative of this substance, 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI-2-C), was also demonstrated in normal urine. A quantitative method was worked out and the normal urinary concentration of this substance was as high as the concentration of 5-S-cysteinyldopa. The concentrations of the eumelanic marker 6-hydroxy-5-methoxyindole-2-carboxylic acid and the pheomelanic marker 5-S-cysteinyldopa were determined in the urine of psoriasis patients during PUVA treatment and also in the urine of subjects with different skin colour. The melanocyte activity in albinotic patients and in albinotic mice was studied by the same technique. Some in vitro experiments were performed to show that 5-S-glutathionyldopa has the molecular properties of forming a mercapto-substituted indole derivative. The following main conclusions were drawn: 1. 5,6-Dihydroxyindole-2-carboxylic acid and 6-hydroxy-5-methoxyindole-2-carboxylic acid are both present in measurable amounts in normal urine. 2. The urinary concentration of 6-hydroxy-5-methoxyindole-2-carboxylic acid increased during PUVA treatment in a similar way as for 5-S-cysteinyldopa. 3. The eumelanic marker 6-hydroxy-5-methoxyindole-2-carboxylic acid was excreted in larger quantities by people with genetically dark skin, whereas the pheomelanic marker 5-S-cysteinyldopa was not related to pigment type. 4. In the urine of one albino patient and in the urine of albinotic mice a total absence of 6-hydroxy-5-methoxyindole-2-carboxylic acid was found. The urinary concentrations of 5-S-cysteinyldopa in these subjects were measurable but lower than in pigmented subjects. Thus, 6-hydroxy-5-methoxy-indole-2-carboxylic acid seems to be a more specific melanocyte marker than the cysteinyldopas.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Albinism; Animals; Biomarkers; Cysteinyldopa; Humans; Indoles; Melanocytes; Mice; Oxidation-Reduction; Pigmentation; PUVA Therapy

The dopa oxidase activity of tyrosinase in the skin from albino and black mice was assayed using a technique based on the formation of two diastereomers of 5-S-cysteinyldopa when incubating tissue extracts with both L-dopa and D-dopa as substrates in the presence of cysteine. The amounts of 5-S-L-cysteinyl-L-dopa and 5-S-L-cysteinyl-D-dopa formed were then determined. In the extract from black mouse skin the L-L-diastereomer was produced in more than ten times the amount of the L-D-diastereomer. This stereospecific dopa-oxidation is indicative of the presence of tyrosinase and corresponds well with earlier determinations of the rates of oxidation for human tyrosinase, using L-dopa and D-dopa as substrates. Stereospecific dopa oxidation was absent in albino skin, and the nonspecific dopa-oxidation was two orders of magnitude less than the dopa oxidation in black skin. The study demonstrates the lack of tyrosinase activity in albino skin, and quantifies the non-specific dopa oxidation. The lack of tyrosinase activity in the eluates from albinotic skin was found not to be due to the presence of a tyrosinase inhibitor.

Topics: Albinism; Animals; Cysteinyldopa; Dihydroxyphenylalanine; Female; In Vitro Techniques; Male; Melanins; Mice; Mice, Inbred C57BL; Monophenol Monooxygenase; Oxidation-Reduction; Skin; Skin Pigmentation; Stereoisomerism

5-S-cysteinyldopa concentrations were determined by high-pressure liquid chromatography and electrochemical detection in plasma from normally pigmented patients and patients with oculocutaneous albinism, both tyrosinase-positive and tyrosinase-negative. The plasma 5-S-cysteinyldopa concentrations were similar in all three groups, suggesting that 5-S-cysteinyldopa can be produced by mechanisms which do not involve tyrosinase.

Topics: Albinism; Animals; Chromatography, High Pressure Liquid; Cysteinyldopa; Dihydroxyphenylalanine; Electrochemistry; Female; Humans; Male; Melanins; Mice; Monophenol Monooxygenase; Rats

The urine of an albino woman contained small quantities of 5-S-cysteinyldopa; 6-hydroxy-5-methoxyindole-2-carboxylic acid, a melanin precursor metabolite, was lacking. The 5-S-cysteinyldopa excretion observed may reflect non-specific oxidation of dopa. Two other albino patients showed normal values for the excretion of 5-S-cysteinyldopa and of 6-hydroxy-5-methoxyindole-2-carboxylic acid.

Topics: Adult; Albinism; Cysteinyldopa; Dihydroxyphenylalanine; Female; Humans; Indoles; Osmolar Concentration; Oxidation-Reduction

Urinary excretion of the phaeomelanin precursor 5-S-cysteinyldopa (5-S-CD) and the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI-2-C) was studied in black and albino mice. The urinary concentration of 5-S-CD was 31.7 ng/ml in black and 16.1 ng/ml in albino mice. The concentration of 6H5MI-2-C was 21.0 ng/ml in the urine of black mice. The compound could not be demonstrated in the urine of albino mice.

Topics: Albinism; Animals; Cysteinyldopa; Female; Indoles; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Reference Values

The clinical, ophthalmological, and biochemical characteristics of a 28-year-old black woman with brown oculocutaneous albinism were determined. Hair color was medium brown and skin color was light brown, and a faint tan developed with sun exposure. The irides were light brown in the central one-third, blue-gray in the peripheral two-thirds, and showed punctate and radial translucency. Visual acuity was 20/60 in the right eye and 20/100 in the left eye. There was a moderate pendular nystagmus, and previous surgeries had corrected an exotropia. The foveal reflex was muted, and the retinal pigment was reduced. Hairbulb tyrosinase activity was 1.75 pmoles/120 min/hairbulb, hairbulb glutathione content 0.83 nmoles/hairbulb, and urine excretion of 5-S-cysteinyldopa 174.9 ng/mg creatinine. Electron microscopy of hairbulb and skin melanocytes showed arrested melanosomal development. These findings suggest that there is a partial block in the distal eumelanin pathway in this form of albinism. The ophthalmological characteristics of six additional cases of this form of albinism are also presented.

Topics: Adult; Albinism; Black People; Cysteinyldopa; Eye; Female; Fundus Oculi; Glutathione; Humans; Microscopy, Electron; Monophenol Monooxygenase; Pedigree; Skin

Topics: Albinism; Animals; Cattle; Choroid; Chromatography, High Pressure Liquid; Cysteinyldopa; Dihydroxyphenylalanine; Kidney; Rats; Retinal Pigments; Skin; Spleen