| First Author | Houten SM | Year | 2012 |
| Journal | J Lipid Res | Volume | 53 |
| Issue | 7 | Pages | 1296-303 |
| PubMed ID | 22534643 | Mgi Jnum | J:186264 |
| Mgi Id | MGI:5431279 | Doi | 10.1194/jlr.M024463 |
| Citation | Houten SM, et al. (2012) Peroxisomal L-bifunctional enzyme (Ehhadh) is essential for the production of medium-chain dicarboxylic acids. J Lipid Res 53(7):1296-303 |
| abstractText | L-bifunctional enzyme (Ehhadh) is part of the classical peroxisomal fatty acid beta-oxidation pathway. This pathway is highly inducible via peroxisome proliferator-activated receptor alpha (PPARalpha) activation. However, no specific substrates or functions for Ehhadh are known, and Ehhadh knockout (KO) mice display no appreciable changes in lipid metabolism. To investigate Ehhadh functions, we used a bioinformatics approach and found that Ehhadh expression covaries with genes involved in the tricarboxylic acid cycle and in mitochondrial and peroxisomal fatty acid oxidation. Based on these findings and the regulation of Ehhadh's expression by PPARalpha, we hypothesized that the phenotype of Ehhadh KO mice would become apparent after fasting. Ehhadh mice tolerated fasting well but displayed a marked deficiency in the fasting-induced production of the medium-chain dicarboxylic acids adipic and suberic acid and of the carnitine esters thereof. The decreased levels of adipic and suberic acid were not due to a deficient induction of omega-oxidation upon fasting, as Cyp4a10 protein levels increased in wild-type and Ehhadh KO mice.We conclude that Ehhadh is indispensable for the production of medium-chain dicarboxylic acids, providing an explanation for the coordinated induction of mitochondrial and peroxisomal oxidative pathways during fasting. |
