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Positional- and stereo-selectivity of fatty acid oxygenation catalysed by mouse (12S)-lipoxygenase isoenzymes.
Bürger, F; Krieg, P; Marks, F; Fürstenberger, G.
Afiliação
  • Bürger F; Research Program Tumor Cell Regulation (B0500), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Biochem J ; 348 Pt 2: 329-35, 2000 Jun 01.
Article em En | MEDLINE | ID: mdl-10816426
A quantitative stereochemical analysis of the products generated by recombinant mouse (12S)-lipoxygenase isoenzymes was performed with arachidonic acid and linoleic acid as substrates. The leucocyte-type (12S)-lipoxygenase generated, in addition to 12-hydroxyeicosatetraenoic acid (12-HETE) as the main product, 15- and 8-HETE from arachidonic acid and 13- and 9-hydroxyoctadecadienoic acid (13- and 9-HODE) from linoleic acid. The platelet-type enzyme oxygenated arachidonic acid to 12- and 8-HETE and linoleic acid to 13- and 9-HODE, whereas the epidermis-type (12S)-lipoxygenase reaction was essentially mono-specific with arachidonic acid but oxygenated linoleic acid to both 13- and 9-HODE. 12-HETE and 13-HODE were almost exclusively the S enantiomers. 8-HETE was the R enantiomer as a side-product of the platelet-type (12S)-lipoxygenase reaction but the S enantiomer as a side-product of the leucocyte-type reaction. 9-HODE was generated as the R enantiomer by the platelet-type and the epidermis-type isoenzymes and as the S enantiomer by the leucocyte-type (12S)-lipoxygenase. On the basis of published models of lipoxygenase-substrate interaction, the stereochemistry of the products generated by the platelet- and epidermis-type (12S)-lipoxygenases is in agreement with a fixed 'tail-to-head' orientation of the substrate fatty acid in the binding pocket of these enzymes, whereas that of the reaction products of the leucocyte-type (12S)-lipoxygenase can be explained only when the inverse orientation of the substrate or a rotational isomerism along the longitudinal axis of the substrate is allowed. Both the product spectra generated and the sensitivity towards the 12-lipoxygenase selective inhibitors N-benzyl-N-hydroxy-4-phenylpentanamide and cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate indicated the platelet-type and the epidermis-type isoenzymes to be biochemically more related to each other than to the leucocyte-type (12S)-lipoxygenase.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Araquidonato 12-Lipoxigenase / Ácidos Linoleicos Conjugados Limite: Animals / Humans Idioma: En Revista: Biochem J Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Araquidonato 12-Lipoxigenase / Ácidos Linoleicos Conjugados Limite: Animals / Humans Idioma: En Revista: Biochem J Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido