@article{vanWeeghelteBrinkevanLentheetal.2012,
  author    = {Michel van Weeghel and Heleen te Brinke and Henk van Lenthe and Wim Kulik and Paul E. Minkler and Maria S. K. Stoll and J{\"o}rn Oliver Sass and Uwe Janssen and Wilhelm Stoffel and K. Otfried Schwab and Ronald J. A. Wanders and Charles L. Hoppel and Sander M. Houten},
  title     = {Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids},
  series   = {FASEB J. (FASEB Journal)},
  volume    = {26},
  number    = {10},
  issn      = {0892-6638},
  doi       = {10.1096/fj.12-206326},
  pages     = {4316 -- 4326},
  year      = {2012},
  abstract  = {Mitochondrial enoyl-CoA isomerase (ECI1) 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 Eci1-deficient knockout (KO) mice to explore a potential presentation of human ECI1 deficiency. Upon food withdrawal, Eci1-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 C12:1 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 C12:1 acylcarnitine levels (WT 0.01 μM vs. KO 0.04 μM, P<0.01). Overall, the phenotypic presentation of Eci1-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Eci1-deficient fibroblasts caused a more pronounced accumulation of C12:1 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 ECI1 deficiency in humans.},
  language  = {en}
}