Integration of amino acid and carbon intermediary metabolism: studies with uniformly labeled tracers and mass isotopomer analysis
| Autor: | Peter D. Klein, Ronna G. Miller, Farook Jahoor, Peter J. Reeds, Linda Wykes, Tamir H. Keshen, Douglas G. Burrin, Tom Jaksic, H. K. Berthold, Barbara Stoll, J. J. Boza |
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| Rok vydání: | 1997 |
| Předmět: |
Mammals
chemistry.chemical_classification Carbon Isotopes Citric Acid Cycle Gluconeogenesis Infant Metabolism Biology Carbon Isotopomers Amino acid Citric acid cycle Metabolic pathway chemistry.chemical_compound Biochemistry chemistry Isotope Labeling Pediatrics Perinatology and Child Health Animals Humans Glycolysis Amino Acids Fatty acid synthesis |
| Zdroj: | European Journal of Pediatrics. 156:S50-S58 |
| ISSN: | 0340-6199 |
| DOI: | 10.1007/pl00014272 |
| Popis: | The central pathways of metabolism include glycolysis and gluconeogenesis, fatty acid synthesis and beta-oxidation, the citric acid cycle and ureagenesis. Because these pathways intersect, changes in one pathway, due to inborn error or disease, affect pathways that may seem remote from the initial metabolic defect. These metabolic interrelationships also present difficulties for isotopic studies, because once carbon derived from isotopic tracers is introduced into metabolism it is extensively recycled. The use of multiple labeled (especially uniformly 13C-labeled ([U-13C]), metabolic tracers, in conjunction with mass isotopomer distribution analysis of mass and nuclear magnetic spectra, has enabled the development of methods that resolve some of these difficulties. Suitable choices of tracers and analytes allow the simultaneous measurement of multiple pathways and, importantly, their kinetic interrelationships. We illustrate three uses of the technique: (1) the unequivocal determination of tracee fluxes; (2) the quantification of biosynthetic pathways; and (3) the dissection, in vivo, of the citric acid (Krebs) cycle. In each case, different combinations of [U-13C]tracer and metabolic end product have revealed metabolic phenomena that otherwise would remain unidentified. A particularly striking, and unexpected, observation that has emerged from recent studies using the technique, suggests that the key dehydrogenase reactions in the Krebs cycle may be reversible. Although this approach is of relatively recent development, it has already given a number of novel insights into the organization of the central metabolic pathways. It should provide a powerful method of investigating the metabolic impact of genetic disease and provide invaluable support of the assessment of new therapeutic interventions. |
| Databáze: | OpenAIRE |
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