NDLI: Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

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Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

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Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jin, Zhicheng Zhang, Guo-fang Brunengraber, Henri Bian, Fang Kelleher, Joanne K. Tomcik, Kristyen
Description	Author Affiliation: Jin Z ( From the Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106 and.); Bian F ( From the Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106 and.); Tomcik K ( From the Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106 and.); Kelleher JK ( the Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.); Zhang GF ( From the Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106 and.); Brunengraber H ( From the Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106 and hxb8@case.edu.)
Abstract	We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully (13)C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the labeling patterns of acetyl-CoA proxies, i.e. total acetyl-CoA, the acetyl moiety of citrate, C-1 + 2 of ß-hydroxybutyrate, malonyl-CoA, and acetylcarnitine. Additional information was obtained from the labeling patterns of citric acid cycle intermediates and related compounds. The data characterize the partial oxidation of DODA and azelate in peroxisomes, with terminal oxidation in mitochondria. We did not find evidence of peroxisomal oxidation of glutarate. Unexpectedly, DODA contributes a substantial fraction to anaplerosis of the citric acid cycle. This opens the possibility to use water-soluble DODA in nutritional or pharmacological anaplerotic therapy when other anaplerotic substrates are impractical or contraindicated, e.g. in propionic acidemia and methylmalonic acidemia.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	30
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-07-24
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Amino Acid Metabolism, Inborn Errors Metabolism Dicarboxylic Acids Liver Metabolism, Inborn Errors Propionic Acidemia Diet Therapy Drug Therapy Genetics Animals Citric Acid Cycle Coenzyme A Fatty Acids Glutarates Pathology Malonyl Coenzyme A Mitochondria Myocardium Oxidation-Reduction Peroxisomes Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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