Tecr, or trans-2-enoyl-CoA reductase, is a key enzyme in very-long-chain fatty acid synthesis. It is involved in the fatty acid elongation cycle, where it catalyzes the reduction reactions in the fourth step of this cycle and in the sphingosine degradation pathway [3,5]. VLCFAs have diverse functions such as in skin barrier formation, liver homeostasis, and myelin maintenance [3].

EC-specific knockout of Tecr in mice shows that it is crucial for angiogenesis as its absence compromises vascular sprouting. Moreover, from neonatal to adult stages, EC-specific deletion of Tecr leads to increased transcytosis and loss of vascular permeability restrictive quality, although vascular tight junctions are maintained. Lipidomic analysis reveals that Tecr expression in endothelial cells is associated with omega-3 fatty acids, which suppress caveolae vesicles formation, thus maintaining blood-brain barrier (BBB) homeostasis [1]. In humans, homozygous TECR variants have been associated with intellectual disability, with the phenotypic spectrum including dolicocephaly and dysgenesis of the corpus callosum [2]. Additionally, a mutation in TECR has been linked to autosomal recessive non-syndromic mental retardation [4].

In conclusion, Tecr is essential for lipid metabolism, especially in the synthesis of very-long-chain fatty acids. Its role in maintaining BBB integrity and its association with intellectual disability highlight its significance in both normal physiological processes and disease conditions. Gene knockout models, like the EC-specific knockout in mice, have been instrumental in uncovering these functions and disease associations [1,2,4].

References:

1. Wang, Jinxuan, Xu, Jianxiong, Zang, Guangchao, Wang, Yeqi, Wang, Guixue. 2022. trans-2-Enoyl-CoA Reductase Tecr-Driven Lipid Metabolism in Endothelial Cells Protects against Transcytosis to Maintain Blood-Brain Barrier Homeostasis. In Research (Washington, D.C.), 2022, 9839368. doi:10.34133/2022/9839368. https://pubmed.ncbi.nlm.nih.gov/35465346/

2. Platt, Dylan, Davis-Keppen, Laura. . Individual with Homozygous TECR Variant Expands Upon the Existing Phenotype for a Hutterite Founder Mutation. In South Dakota medicine : the journal of the South Dakota State Medical Association, 75, 150-153. doi:. https://pubmed.ncbi.nlm.nih.gov/35709344/

3. Zhou, Youli, Lv, Rui, Ye, Richard D, Ren, Ruobing, Yu, Leiye. 2024. The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with trans-2-enoyl-CoA reductase involved in substrates transfer in very long chain fatty acid elongation. In Biochemical and biophysical research communications, 704, 149588. doi:10.1016/j.bbrc.2024.149588. https://pubmed.ncbi.nlm.nih.gov/38422897/

4. Çalışkan, Minal, Chong, Jessica X, Uricchio, Lawrence, Nicolae, Dan L, Ober, Carole. 2011. Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. In Human molecular genetics, 20, 1285-9. doi:10.1093/hmg/ddq569. https://pubmed.ncbi.nlm.nih.gov/21212097/

5. Kato, Ryoya, Takenaka, Yuka, Ohno, Yusuke, Kihara, Akio. 2024. Catalytic mechanism of trans-2-enoyl-CoA reductases in the fatty acid elongation cycle and its cooperative action with fatty acid elongases. In The Journal of biological chemistry, 300, 105656. doi:10.1016/j.jbc.2024.105656. https://pubmed.ncbi.nlm.nih.gov/38224948/