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Catalytic turnover dependent modification of the Pseudomonas aeruginosa heme oxygenase (pa-HO) by 5,6-O-isopropyledine-2-O-allyl-ascorbic acid.
Bhakta, Mehul N; Olabisi, Ayodele; Wimalasena, Kandatege; Wilks, Angela.
Afiliación
  • Bhakta MN; Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 Penn Street, Baltimore, MD 21201, US.
J Inorg Biochem ; 102(2): 251-9, 2008 Feb.
Article en En | MEDLINE | ID: mdl-17923157
Heme oxygenase (HO) catalyzes the NADPH dependent conversion of heme to biliverdin with the release of iron and CO via three successive oxygenation steps. The oxidation of heme in the presence of alternate reductants, such as ascorbic acid, has been used extensively to characterize the mechanism of oxygen activation in HO without altering the chemistry of the reaction. NADPH-dependent cytochrome P450 reductase (CPR) and ascorbic acid mediated reactions are mechanistically very similar, in that both use molecular oxygen to initiate the reaction. In the present manuscript, we report on an ascorbic acid derivative, 5,6-O-isopropyledine-2-O-allyl-ascorbic acid, that during catalysis partitions the reaction between the conversion of heme to biliverdin, and an alternate pathway that traps the verdoheme intermediate as a result of protein modification. We propose that following activation of 5,6-O-isopropyledine-2-O-allyl-ascorbic acid to the cation radical, protein modification results via alkylation of an active site nucleophile (Asp or Glu), trapping the Fe(III)-verdoheme intermediate. The potential site of the modification and the relevance to the mechanism of Fe(III)-verdoheme conversion to biliverdin is discussed.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Ácido Ascórbico / Biliverdina / Compuestos Alílicos / Hemo Oxigenasa (Desciclizante) Idioma: En Revista: J Inorg Biochem Año: 2008 Tipo del documento: Article Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Ácido Ascórbico / Biliverdina / Compuestos Alílicos / Hemo Oxigenasa (Desciclizante) Idioma: En Revista: J Inorg Biochem Año: 2008 Tipo del documento: Article Pais de publicación: Estados Unidos