615-91-8Relevant articles and documents
Chemical simulation of biogenesis of the 2,4,5-trihydroxyphenylalanine quinone cofactor of copper amine oxidases: Mechanistic distinctions point toward a unique role of the active site in the o-quinone water addition step
Mandal, Subrata,Lee, Younghee,Purdy, Matthew M.,Sayre, Lawrence M.
, p. 3574 - 3584 (2000)
The biogenesis of the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor from tyrosine at the active site of copper amine oxidases is believed to proceed along a pathway that includes a conjugate addition of water to the corresponding o-quinone intermediate, followed by autoxidation of the resulting benzenetriol to the hydroxyquinone cofactor. The water addition reaction has been presumed to occur not only in previous model studies reported for cofactor biogenesis starting with either catechol or o-quinone, but also for generation of the neurotoxin 6-hydroxydopamine during autoxidation of dopamine. We here report the surprising finding that water addition does not occur under solution chemistry conditions. The production of hydroxyquinone from catechol arises instead from reaction of the o-quinone with H2O2 generated during autoxidation of catechol. When starting with the o-quinone itself, production of hydroxyquinone still arises from autoxidation of the catechol, generated either by reduction of the o-quinone by its decomposition products at moderate pH, or by a novel base-mediated redox disproportionation of the o-quinone at high pH. These conclusions are supported by the behavior of independently studied o-quinone intermediates, the observed effects of added catalase, and 18O-labeling studies utilizing both [18O]H2O and [18O]O2. The failure to observe water addition to the o-quinone has broad implications for aqueous o-quinone chemistry, and suggests that in TPQ biogenesis, this hydration is being catalyzed at the enzyme active site, possibly by the bound copper.
Generation of the Neurotoxin 6-Hydroxydopamine by Peroxidase/H2O2 Oxidation of Dopamine
Napolitano, Alessandra,Crescenzi, Orlando,Pezzella, Alessandro,Prota, Giuseppe
, p. 917 - 922 (2007/10/02)
At physiological pH values, oxidation of the neurotransmitter dopamine(DA) by the peroxidase/H2O2 system leads to, besides dopaminochrome and 5,6-dihydroxyindole resulting from oxidative cyclization of dopaminequinone (DQ), significant amounts of the neurotoxin 6-hydroxydopamine (6-OHDA) in the oxidized quinonoid form (topaminequinone, TQ).Formation of TQ was shown to depend critically on the presence of hydrogen peroxide in the reaction medium and was not observed when DA oxidation was carried out using the tyrosinase/O2 system or chemical agents such as periodate or ferricyanide.These and other data suggest that, under the conditions adopted, nucleophilic attack of the hydrogen peroxide anion on DQ leading to TQ significantly competes with the intramolecular cyclization path.In line with this mechanism, the reaction course was not affected by the presence of hydroxyl radical scavengers.Peroxidase/H2O2 oxidation of the model N-acetyldopamine (1) gave, as expected, the 2-hydroxy-1,4-benzoquinone 3 in yields up to 55percent, depending on the catecholamine/H2O2 mole ratio.Likewise, reaction of 4-methyl-1,2-benzoquinone (4) with hydrogen peroxide afforded 2-hydroxy-5-methyl-1,4-benzoquinone (5) in good yields.Collectively, these results would point to the possibility that intraneuronal formation of 6-OHDA is associated with an increased production of hydrogen peroxide under oxidative stress conditions.
