A mechanism for the formation in vivo of the 8-methyl ether of xanthurenic acid in humans. |
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| Authors: | J E Leklem R R Brown L V Hankes C R Jansen |
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| Affiliation: | 1. Department of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7, Budapest H-1092, Hungary;2. MS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest H-1117, Hungary;3. SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Semmelweis University, Nagyvárad tér 4, Budapest H-1089, Hungary;4. Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvárad tér 4, Budapest H-1089, Hungary;5. MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyvárad tér 4, Budapest H-1089, Hungary;1. Department of Clinical Medicine, Aarhus University, Denmark;2. Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Denmark;3. Hammel Neurorehabilitation Centre and University Research Clinic, Denmark;4. Department of Forensic Medicine, Aarhus University, Denmark;1. Department of Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey;2. Department of Medical Laboratory Techniques, Selcuk University Vocational School of Health, Konya, Turkey |
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| Abstract: | The mechanism of formation of the tryptophan metabolite, xanthurenic acid 8-methyl ether, has been open to question since it was shown to occur in the urine of humans. To investigate possible pathways, human subjects were given l-methionine-methyl-14C, l-kynurenine-keto-14C, 3-hydroxy-l-kynurenine-keto-14C, or xanthurenic acid-4-14C. Analysis of urine by ion exchange chromatography, paper chromatography and carier isolations showed that the methyl group of xanthurenic acid 8-methyl ether came from l-methionine-methyl-14C. The xanthurenic acid 8-methyl ether accounted for 0.005–0.038% of the dose of l-methionine-methyl-14C. Keto-14C labeled l-kynurenine and 3-hydroxy-l-kynurenine were both converted to xanthurenic acid 8-methyl ether, but accounted for only 0.015 and 0.028% of the dose, respectively. Xanthurenic acid-4-14C also gave rise to labeled xanthurenic acid 8-methyl ether in four human subjects, with this metabolite accounting for 0.045–0.15% of the dose. No urinary 3-methoxykynurenine was detected, but labeled 3-methoxyanthranilic acid (from l-methionine-methyl-14C) was detected. These data indicate that xanthurenic acid may be methylated directly to form xanthurenic acid 8-methyl ether in humans. Since 3-methoxykynurenine could not be detected, it is suggested that 3-methoxyanthranilic acid is formed by methylation of 3-hydroxyanthranilic acid rather than from 3-methoxykynurenine, although the transient presence of the latter cannot be excluded. |
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