Unformatted text preview: n the absence of cysteine, dopaquinone undergoes the addition of the amino group giving cyclodopa (leucodopachrome). The redox exchange between leucodopachrome and dopaquinone then gives rise to dopachrome (and dopa). Dopachrome gradually decomposes to give mostly DHI, and to a lesser extent DHICA. This latter process is catalysed by DCT. Finally, these dihydroxyindoles are oxidized to eumelanin: DHI oxidizes spontaneously (or faster with tyrosinase action); DHICA transformation is slower but needs TYRP1 catalysis. B) In the presence of cysteine, dopaquinone rapidly reacts with cysteine to give 5‐S‐
cysteinyldopa and to a lesser extent 2‐S‐cysteinyldopa. Cysteinyldopas are then oxidized to give benzothiazine intermediates and finally to produce pheomelanin (adapted from ). Melanogenesis takes place in the speed melanocyte organelles known as melanosomes , where the pigment is synthesised and “packaged”. The melanosomes are then transported to the adjacent keratinocytes via dendritic cytoplasmic extensions. Four morphologically distinctive stages are observed that correlate with successive stages of melanosome ‘maturation’ and biogenesis: 12 Chapter I – Thesis Overview stages I and II are described as non‐pigmented immature pre‐melanosomes; whereas stages III and IV melanosomes are capable of melanogenesis (Figure 1.1.7.) [88‐91]. Figure 1.1.7. Melanosome biogenesis, maturation and secretion. Melanosome stages I through IV are indicated. Non‐pigmented stage I melanosomes contain the melanosomal protein Pmel17 sorted into intralumenal vesicles, and MART1. Stage II melanosomes are characterised by Pmel17 undergoing proteolytic cleavage, forming intralumenal fibrillar striations. The melanogenic enzymes TYR and TYRP1 are delivered to preformed stage II melanosomes from early endosomes or transport vesicles from Golgi complex which marks transition into stage III (adapted from ). Stage I melanosomes are vacuolar early endosomes. Premelanosome protein PMEL plays an essential role in the structural organization of premelanosomes: in stage I melanosomes it is sorted into intralumenal vesicles, and later it undergoes proteolytic cleavage to generate intralum...
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