Understanding cerebral L-lysine metabolism: the role of L-pipecolate metabolism in Gcdh-deficient mice as a model for glutaric aciduria type I
| Autor: | Silvana Opp, Georg F. Hoffmann, Roland Posset, Stefan Kölker, Jürgen G. Okun, Sven W. Sauer, Alfred Völkl, Eduard A. Struys, Heribert Mohr |
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| Přispěvatelé: | Clinical chemistry, NCA - Brain mechanisms in health and disease |
| Rok vydání: | 2014 |
| Předmět: |
Biology
complex mixtures chemistry.chemical_compound Peroxisomes Genetics Animals Genetic Predisposition to Disease Amino Acid Metabolism Inborn Errors Genetics (clinical) Pipecolic acid Mice Knockout chemistry.chemical_classification Oxidoreductases Acting on CH-NH Group Donors Oxidase test Glutaryl-CoA Dehydrogenase Brain Diseases Metabolic Catabolism Lysine Glutaric aciduria Brain Metabolism Peroxisome Amino acid Disease Models Animal Phenotype Liver Biochemistry chemistry Deamination Saccharopine Pipecolic Acids bacteria Oxidation-Reduction |
| Zdroj: | Journal of Inherited Metabolic Disease, 38(2), 265-272. Springer Netherlands Posset, R, Opp, S, Struys, E A, Volkl, A, Mohr, H, Hoffmann, G F, Kolker, S, Sauer, S W & Okun, J G 2015, ' Understanding cerebral L-lysine metabolism: the role of L-pipecolate metabolism in Gcdh-deficient mice as a model for glutaric aciduria type I ', Journal of Inherited Metabolic Disease, vol. 38, no. 2, pp. 265-272 . https://doi.org/10.1007/s10545-014-9762-z |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1007/s10545-014-9762-z |
| Popis: | Inherited deficiencies of the L-lysine catabolic pathway cause glutaric aciduria type I and pyridoxine-dependent epilepsy. Dietary modulation of cerebral L-lysine metabolism is thought to be an important therapeutic intervention for these diseases. To better understand cerebral L-lysine degradation, we studied in mice the two known catabolic routes -- pipecolate and saccharopine pathways -- using labeled stable L-lysine and brain peroxisomes purified according to a newly established protocol. Experiments with labeled stable L-lysine show that cerebral L-pipecolate is generated along two pathways: i) a minor proportion retrograde after ε-deamination of L-lysine along the saccharopine pathway, and ii) a major proportion anterograde after α-deamination of L-lysine along the pipecolate pathway. In line with these findings, we observed only little production of saccharopine in the murine brain. L-pipecolate oxidation was only detectable in brain peroxisomes, but L-pipecolate oxidase activity was low (7 ± 2μU/mg protein). In conclusion, L-pipecolate is a major degradation product from L-lysine in murine brain generated by α-deamination of this amino acid. |
| Databáze: | OpenAIRE |
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