Compartmentation of metabolism of the C12-, C9-, and C5-n-dicarboxylates in rat liver, investigated by mass isotopomer analysis: Anaplerosis from dodecanedioate
Jin, Z; Bian, F; Tomcik, K; Kelleher, JK; Zhang, GF; Brunengraber, H
HERO ID
2902038
Reference Type
Journal Article
Year
2015
Language
English
PMID
| HERO ID | 2902038 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Compartmentation of metabolism of the C12-, C9-, and C5-n-dicarboxylates in rat liver, investigated by mass isotopomer analysis: Anaplerosis from dodecanedioate |
| Authors | Jin, Z; Bian, F; Tomcik, K; Kelleher, JK; Zhang, GF; Brunengraber, H |
| Journal | Journal of Biological Chemistry |
| 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 vs 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 β-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. |
| Doi | 10.1074/jbc.M115.651737 |
| Pmid | 26070565 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |