CD isomers transform to BTCA, BZ, ODHBT

Stable Identifier
R-HSA-5662904
Type
Reaction [transition]
Species
Homo sapiens
Compartment
melanosome lumen
Synonyms
5-S-cysteinyldopa + L-dopaquinone => 5-S-cysteinyldopaquinone + L-dopa
ReviewStatus
5/5
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CD isomers transform to BTCA, BZ, ODHBT
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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
12049796 Metal ions as potential regulatory factors in the biosynthesis of red hair pigments: a new benzothiazole intermediate in the iron or copper assisted oxidation of 5-S-cysteinyldopa

Di Donato, P, Napolitano, A, Prota, G

Biochim. Biophys. Acta 2002
Characterisation of 1,4-benzothiazine intermediates in the oxidative conversion of 5-S-cysteinyldopa to pheomelanins

Napolitano, A, Costantini, C, Crescenzi, O, Prota, G

Tetrahedron Letters 1994
18435615 The "benzothiazine" chromophore of pheomelanins: a reassessment

Napolitano, A, De Lucia, M, Panzella, L, d'Ischia, M

Photochem. Photobiol. 2008
10806337 New regulatory mechanisms in the biosynthesis of pheomelanins: rearrangement vs. redox exchange reaction routes of a transient 2H-1, 4-benzothiazine-o-quinonimine intermediate

Napolitano, A, Di Donato, P, Prota, G

Biochim. Biophys. Acta 2000
10952395 Spontaneous redox reactions of dopaquinone and the balance between the eumelanic and phaeomelanic pathways

Land, EJ, Riley, PA

Pigment Cell Res. 2000
19493317 Chemical analysis of late stages of pheomelanogenesis: conversion of dihydrobenzothiazine to a benzothiazole structure

Wakamatsu, K, Ohtara, K, Ito, S

Pigment Cell Melanoma Res 2009
12950733 1,4-benzothiazines as key intermediates in the biosynthesis of red hair pigment pheomelanins

Di Donato, P, Napolitano, A

Pigment Cell Res. 2003
10490271 Transient quinonimines and 1,4-benzothiazines of pheomelanogenesis: new pulse radiolytic and spectrophotometric evidence

Napolitano, A, Di Donato, P, Prota, G, Land, EJ

Free Radic. Biol. Med. 1999
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Cross References
RHEA
Authored
Jupe, S  (2015-01-13)
Reviewed
Ito, S  (2015-02-13)
d'Ischia, M  (2015-02-13)
Created
Jupe, S  (2015-01-14)
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