Characterization of carnitine and fatty acid metabolism in the long-chain acyl-CoA dehydrogenase-deficient mouse
| Autor: | Albert H. Bootsma, Frédéric M. Vaz, Willem Kulik, Liqun Tian, Ronald J.A. Wanders, H. Overmars, Philip A. Wood, Naomi van Vlies |
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| Přispěvatelé: | Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Cardiomyopathy Dehydrogenase Mice Inbred Strains Biology Kidney Biochemistry Long-chain acyl-CoA dehydrogenase chemistry.chemical_compound Mice Internal medicine Carnitine Testis medicine Animals Acetylcarnitine Molecular Biology Brain Chemistry Fatty acid metabolism Muscles Acyl-CoA Dehydrogenase Long-Chain Fatty Acids Cell Biology medicine.disease Endocrinology chemistry Liver Carnitine biosynthesis Flux (metabolism) medicine.drug Research Article |
| Zdroj: | Biochemical journal, 387(Part 1), 185-193. Portland Press Ltd. |
| ISSN: | 0264-6021 |
| DOI: | 10.1042/bj20041489 |
| Popis: | In the present paper, we describe a novel method which enables the analysis of tissue acylcarnitines and carnitine biosynthesis intermediates in the same sample. This method was used to investigate the carnitine and fatty acid metabolism in wild-type and LCAD−/− (long-chain acyl-CoA dehydrogenase-deficient) mice. In agreement with previous results in plasma and bile, we found accumulation of the characteristic C14:1-acylcarnitine in all investigated tissues from LCAD−/− mice. Surprisingly, quantitatively relevant levels of 3-hydroxyacylcarnitines were found to be present in heart, muscle and brain in wild-type mice, suggesting that, in these tissues, long-chain 3-hydroxyacyl-CoA dehydrogenase is rate-limiting for mitochondrial β-oxidation. The 3-hydroxyacylcarnitines were absent in LCAD−/− tissues, indicating that, in this situation, the β-oxidation flux is limited by the LCAD deficiency. A profound deficiency of acetylcarnitine was observed in LCAD−/− hearts, which most likely corresponds with low cardiac levels of acetyl-CoA. Since there was no carnitine deficiency and only a marginal elevation of potentially cardiotoxic acylcarnitines, we conclude from these data that the cardiomyopathy in the LCAD−/− mouse is caused primarily by a severe energy deficiency in the heart, stressing the important role of LCAD in cardiac fatty acid metabolism in the mouse. |
| Databáze: | OpenAIRE |
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