The metabolism of D- and L-3-hydroxybutyrate in developing rat brain |
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| Authors: | K R Swiatek G J Dombrowski K L Chao |
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| Affiliation: | 1. Illinois Institute for Developmental Disabilities, 1640 West Roosevelt Road, Chicago, Illinois 60680 USA;2. Institute for the Study of Developmental Disabilities, Chicago, Illinois 60680 USA;3. Department of Biological Sciences, University of Illinois, Chicago, Illinois 60680 USA;1. Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, PR China;2. Department of Organic Device Engineering, Research Center for Organic Electronics, Yamagata University, Yonezawa 992-8510, Japan;1. Department of Environmental Health, Harvard T.H. Chan School of Public Health and MD-PhD Program, Harvard Medical School, Boston, MA, USA;2. Department of Environmental Health and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;3. Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY, USA;1. Laboratory of Biomolecular Science, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan;2. Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;3. Medicinal Research Laboratories, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan;4. Shiseido Co., Ltd, 1-1-16 Higashi-shimbashi, Minato-ku, Tokyo 105-0021, Japan;5. Department of Drug Discovery and Evolution, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan |
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| Abstract: | The incorporation of L- and D-3-hydroxybutyrate into rat brain protein, lipid, and amino acids during development was studied. L-3-Hydroxybutyrate was found to label brain protein and amino acids in addition to sterols and fatty acids throughout the first 32 postnatal days. Age related changes in L- and D-3-hydroxybutyrate labeling of protein and amino acids were similar. Whereas L-3-hydroxybutyrate incorporation into brain lipids rose sharply between 6-15 days of age, D-3-HOB incorporation into the lipid fraction gradually increased from birth through the age of 15 days. Incorporation by both isomers into lipid was greatest during the third week of suckling and then declined when the animals were weaned. At 15 days of age, the distribution of L-3-hydroxybutyrate into glutamate, glutamine + aspartate, and gamma-aminobutyrate was similar to that obtained with D-3-hydroxybutyrate. L-3-Hydroxybutyrate was poorly oxidized to CO2 by brain slices and mitochondria. Oxidation capacity was maximal from 15-21 days of age for both isomers. The activity of L-3-hydroxybutyrl-CoA ligase increased between 6-28 days of age, and its increase is well correlated with the developmental pattern of L-3-hydroxybutyrate incorporation and mitochondrial oxidation. L-3-Hydroxybutyrate was not detected in the blood of palmitate-injected pups or fasted adult animals. These results suggest that although L-3-hydroxybutyrate can be utilized for the synthesis of brain components during development, its negligible blood concentration precludes a significant contribution to either tissue synthesis or energy balance during the suckling period. |
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