Xanthurenic acid inhibits metal ion-induced lipid peroxidation and protects NADP-isocitrate dehydrogenase from oxidative inactivation.

Vitamin B6 deficiency increases the lipid peroxidation and the synthesis of xanthurenic acid from tryptophan. Antioxidant properties of xanthurenic acid were examined in relation to the coordination of transition metals. Xanthurenic acid inhibited the formation of thiobarbituric acid-reactive substances as a marker of iron-mediated lipid peroxidation and copper-dependent oxidation of low density lipoprotein. NADP-isocitrate dehydrogenase (EC 1.1.1.42), a principal NADPH-generating enzyme for the antioxidant defense system, was inactivated by reduced iron and copper, and xanthurenic acid protected the enzyme from the Fe2+-mediated inactivation. Xanthurenic acid may participate in the enhanced regeneration of reduced glutathione by stimulating the NADPH supply. Xanthurenic acid further enhanced the autooxidation of Fe2+ ion. Other tryptophan metabolites such as kynurenic acid and various quinoline compounds did not inhibit the lipid peroxidation and the inactivation of NADP-isocitrate dehydrogenase, and they showed little or no effect on the Fe2+ autooxidation. The antioxidant properties of xanthurenic acid are related to the metal-chelating activity and probably to the enhanced oxidation of reduced transition metals as a prooxidant, and this action may be due to the electron deficient nature of this compound.

[1]  R. Tsubouchi,et al.  Antioxidant and Prooxidant Actions of Gallic Acid Derivatives: Effect on Metal-dependent Oxidation of Lipids and Low Density Lipoprotein , 2000 .

[2]  K. Murakami,et al.  Dipicolinic Acid as an Antioxidant: Protection of Glutathione Reductase from the Inactivation by Copper , 1999 .

[3]  H. Malina.  Xanthurenic acid provokes formation of unfolded proteins in endoplasmic reticulum of the lens epithelial cells. , 1999, Biochemical and biophysical research communications.

[4]  L. Landi,et al.  Vitamin B6 deficiency affects antioxidant defences in rat liver and heart , 1998, Biochemistry and molecular biology international.

[5]  K. Murakami,et al.  ANTIOXIDANT EFFECT OF DIPICOLINIC ACID ON THE METAL-CATALYZED LIPID PEROXIDATION AND ENZYME INACTIVATION , 1998 .

[6]  K. Murakami,et al.  Interaction of iron with polyphenolic compounds: application to antioxidant characterization. , 1998, Analytical biochemistry.

[7]  Malina Hz,et al.  3-hydroxykynurenine transamination leads to the formation of the fluorescent substances in human lenses. , 1996 .

[8]  H. Malina,et al.  3-hydroxykynurenine transamination leads to the formation of the fluorescent substances in human lenses. , 1996, European journal of ophthalmology.

[9]  R. Schwarcz,et al.  Molecular cloning of rat kynurenine aminotransferase: Identity with glutamine transaminase K , 1994, FEBS letters.

[10]  R. Colman,et al.  Identification of metal-isocitrate binding site of pig heart NADP-specific isocitrate dehydrogenase by affinity cleavage of the enzyme by Fe(2+)-isocitrate. , 1993, The Journal of biological chemistry.

[11]  V. Ravichandran,et al.  Increased lipid peroxidation in kidney of vitamin B-6 deficient rats. , 1990, Biochemistry international.

[12]  H. H. Draper,et al.  Malondialdehyde determination as index of lipid peroxidation. , 1990, Methods in enzymology.

[13]  M. Tobes.  [28] Kynurenine-oxoglutarate aminotransferase from rat kidney , 1987 .

[14]  S. Williams,et al.  Quantitation of xanthurenic acid in rabbit serum using high performance liquid chromatography. , 1984, The American journal of clinical nutrition.

[15]  G. Allegri,et al.  Alterations of the tryptophan--nicotinic acid metabolism in vitiligo. , 1982, Acta vitaminologica et enzymologica.

[16]  N. Ogasawara,et al.  Kynurenine-transaminase, kynureninase and the increase of xanthurenic acid excretion. , 1962, Journal of biochemistry.