Quinone Chemistry and Melanogenesis

The divergence of the melanogenic pathway occurs after the initial oxidation step that yields dopaquinone. The current analytical approach to the classification of melanins depends on the assessment of the comparative levels of degradation products that are considered characteristic of indoles and benzothiazine residues. Several physical methods for the analysis of melanins are available, including solid-state nuclear magnetic resonance (NMR) spectroscopy using 13C and 15N as probes, and electron paramagnetic resonance (EPR) spectroscopy. The most reliable method of quantitative analysis of eumelanins and pheomelanins relies on chemical degradation and high-performance liquid chromatography (HPLC) separation of the degradation products. The basis of this method is the yield of (1) pyrrole-2, 3, 5-tricarboxylic acid (PTCA) from 5, 6-dihydroxyindole-2-carboxylic acid (DHICA) (2.8%) and 5, 6-dihydroxyindole (DHI) (0.03%) after permanganate oxidation as an indication of eumelanin and (2) aminohydroxyphenylalanine (AHP) from benzothiazine derivatives by hydriodic acid hydrolysis as an indicator of pheomelanin content. These products are separated by HPLC and quantified by ultraviolet (UV) detection. Three important alternative modes of reaction of ortho-quinones in biological systems can be identified: (1) addition, (2) reduction, and (3) tautomerism. These pathways are illustrated in the chapter with selected examples.