Dopachrome tautomerase

Figure 1. The biosynthetic pathway from tyrosine to melanin (according to Hearing and Tsukamoto, 1991 Tsukamoto et al., 1992). Tyrosinase catalyzes three different reactions in this pathway (1, 2, 3). The reaction catalyzed by the product of TRP-2, DOPAchrome tautomerase, is indicated by 4. DOPA = 3,4-dihydroxyphenylalanine DHICA = 5,6-dihydroxyin-dole-2-carboxylic acid DHI = 5,6-dihydroxyindole.

Tsukamoto, K., Jackson, I. J., Urabe, K., Montague, P. M., and Hearing, V. J. (1992). A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase. EMBO J. 11 519-526. 

Ty initiates melanin synthesis by the hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (Dopa) and the oxidation of dopa to dopaquinone. In the presence of L-cysteine, dopaquinone rapidly combines with the thiol group to form cysteinyldopas, which undergo nonen-zymatic conversion and polymerization to pheomelanin via benzothiazine intermediates. In the absence of thiol groups, dopaquinone very rapidly undergoes conversion to dopachrome, which is transformed to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) by dopachrome tautomerase. Alternatively, dopachrome is converted nonenzymatically to 5,6-dihydroxyindole (DHI). Oxidation of DHICA and DHI to the corresponding quinones and subsequent polymerization leads to eumelanins. It is still questionable if Ty is involved in this step. 

Homo sapiens D-dopachrome tautomerase (DDT) gene, exon 1. AF012432... 

Further, recent studies 132) have revealed the presence in melanocytes of a melanosomal protein different from tyrosinase, which has the ability to catalyze the rearrangement of dopachrome to DHICA. This enzymic reaction is highly stereospecific for normal L-dopachrome, is unaffected by metal chelators and has an optimal pH of about 6.8. Different names have been proposed for this enzyme, i.e. dopachrome conversion factor 132, 256), dopachrome oxidoreductase 143), dopachrome isomerase 201), and dopachrome tautomerase 4). It is of interest that another enzyme named dopaquinoneimine conversion factor seems to exist which has the remarkable ability to catalyze the decaibox-ylative rearrangement of dopachrome to DHI rather than DHICA 193). 

Aroca P, Garcia-Borron JC, Solano F, Lozano JA (1990) Regulation of Distal Mammalian Melanogenesis. 1 Partial Purification and Characterization of a Dopa-chrome Converting Factor Dopachrome Tautomerase. Biochim Biophys Acta 1035 266... 

Pennock JL, Behnke JM, Bickle QD, Devaney E, Grends RK, Isaac RE, Joshua GWR Selkirk ME, Zhang Y, Meyer DJ (1998) Rapid purification and characterization of L-dopachrome-methyl ester tautomerase (macrophage-migration-inhibitory factor) from Trichinella spiralis, Trichuris muris and Brugia pahangi. Biochem J 335 495 98... 

---