CD isomers transform to BT, BTCA, BZ, ODHBT

Stable Identifier
R-HSA-5662904
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Following the formation of cysteinyldopa (CD) isomers, pheomelanogenesis continues with the redox exchange of CD isomers with dopaquinone (DQ), generating cysteinyldopaquinone (CDQ). Once formed, CDQ rapidly cyclizes via attack of the cysteinyl side-chain amino group on the carbonyl group to produce a cyclic ortho-quinonimine intermediate (QI) (Napolitano et al. 1994, Land & Riley 2000). Redox exchange between CD and QI leads to the production of a reduced form of QI, 3,4-dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA) and CDQ (Napolitano et al. 2000, Wakamatsu et al. 2009). QI rapidly undergoes rearrangement, with or without decarboxylation, leading to 2H-1,4-benzothiazine (BT) and its 3-carboxy derivative, 2H-1,4-benzothiazine-3-carboxylic acid (BTCA) (Napolitano et al. 1994, 2008). The ratio of BT to BTCA depends on many factors including the pH of the medium and the presence or absence of metal ions (Di Donato et al. 2002, Napolitano et al. 2000). BT and BTCA are unstable, decaying in seconds. Modifications of the benzothiazine moiety of BT and BTCA lead to the formation of 3-oxo-3,4-dihydro-1,4-benzothiazine (ODHBT) and benzothiazole (BZ) (Napolitano et al. 1999, 2008).

The reactions beyond BT and BTCA which ultimately lead to the production of pheomelanin appear to be very complex (Di Donato & Napolitano 2003). Zn2+ promotes retention of the carboxyl group in BTCA while Fe3+ accelerates the ring contraction of BT to BZ (Di Donato et al. 2002). Production of ODHBT is increased by the presence of hydrogen peroxide (Di Donato et al. 2002).

Literature References
PubMed ID Title Journal Year
10952395 Spontaneous redox reactions of dopaquinone and the balance between the eumelanic and phaeomelanic pathways

Land, EJ, Riley, PA

Pigment Cell Res. 2000
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