MECR Human

The MECR gene consists of 10 exons and spans more than 37 kilobases . The protein encoded by this gene is an oxidoreductase that catalyzes the NADPH-dependent reduction of trans-2-enoyl-CoA to acyl-CoA with chain lengths ranging from C6 to C16 . The enzyme has a calculated molecular mass of approximately 37 kilodaltons and forms homodimers with a native mass of about 65 kilodaltons .

MECR is expressed at the highest levels in skeletal and heart muscle, with weaker expression in the brain, placenta, liver, kidney, and pancreas . The enzyme displays a preference for medium-chain substrates and is involved in the synthesis of lipoic acid, which is crucial for protein lipoylation and mitochondrial respiratory activity . The enzyme accepts both acyl carrier protein (ACP) and CoA thioesters as substrates in vitro .

Mutations in the MECR gene have been associated with childhood-onset dystonia, optic atrophy, and basal ganglia abnormalities . These mutations result in reduced levels of MECR protein and a significant decrease in protein lipoylation, leading to mitochondrial dysfunction . The enzyme’s role in mitochondrial fatty acid synthesis and its involvement in various metabolic pathways highlight its importance in maintaining cellular energy homeostasis.

Recombinant MECR has been successfully cloned and expressed in various systems. The recombinant protein has been shown to restore mitochondrial respiratory function in yeast strains deficient in 2-enoyl thioester reductase . This demonstrates the enzyme’s potential for therapeutic applications in conditions related to mitochondrial dysfunction.