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- Title
Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids.
- Authors
Van Weeghel, Michel; Te Brinke, Heleen; Van Lenthe, Henk; Kulik, Wim; Minkler, Paul E.; Stoll, Maria S. K.; Sass, Jorn Oliver; Janssen, Uwe; Stoffel, Wilhelm; Schwab, K. Otfried; Wanders, Ronald J. A.; Hoppel, Charles L.; Houten, Sander M.
- Abstract
Mitochondrial enoyl-CoA isomerase (ECU) is an auxiliary enzyme involved in unsaturated fatty acid oxidation. In contrast to most of the other enzymes involved in fatty acid oxidation, a deficiency of ECI1 has yet to be identified in humans. We used wild-type (WT) and Ecil-deficient knockout (KO) mice to explore a potential presentation of human ECU deficiency. Upon food withdrawal, Ecil-deficient mice displayed normal blood β-hydroxybutyrate levels (WT 1.09 mM vs. KO 1.10 mM), a trend to lower blood glucose levels (WT 4.58 mM vs. KO 3.87 mM, P=0.09) and elevated blood levels of unsaturated acylcarnitines, in particular C12:l acylcarnitine (WT 0.03 µM vs. KO 0.09 µM, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12:l acylcarnitine levels (WT 0.01 oM vs. KO 0.04 µM, P<0.01). Overall, the phenotypic presentation of Ecil-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Ecil-deficient fibroblasts caused a more pronounced accumulation of C12:l acylcarnitine on incubation with unsaturated fatty acids (12-fold, P<0.05). We conclude that Eci2 compensates for Eci1 deficiency explaining the mild phenotype of Eci1-deficient mice. Hypoglycemia and accumulation of C12:1 acylcarnitine might be diagnostic markers to identify ECU deficiency in humans.
- Subjects
ISOMERASES; METABOLIC disorders; UNSATURATED fatty acids; OXIDATION; ENZYMES
- Publication
FASEB Journal, 2012, Vol 26, Issue 10, p4316
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.12-206326