ENO3

ENO3, also known as beta-enolase, is a protein-coding gene that encodes the muscle-specific isoform of the glycolytic enzyme enolase. Enolases catalyze the reversible dehydration of 2-phosphoglycerate to phosphoenolpyruvate, a step in glycolysis that ultimately contributes to ATP production in cells. ENO3 belongs to a small family of enolase genes, including ENO1 (ubiquitous) and ENO2 (neuron-specific), which share sequence similarity and catalytic function but have distinct tissue distributions.

In humans, ENO3 expression is predominantly found in skeletal muscle, with some expression in cardiac muscle. The encoded beta-enolase subunit forms functional enolase as part of a homodimer in the cytosol. Regulation of ENO3 expression is linked to muscle activity, development, and metabolic demand, reflecting the reliance of contracting muscle on glycolytic energy pathways.

Clinical significance of ENO3 is most clearly demonstrated by rare cases of beta-enolase deficiency. Variants in ENO3 can lead to reduced enzymatic activity in skeletal muscle, causing exercise intolerance, muscle cramps, fatigue, and, in some cases, myoglobinuria after strenuous activity. Diagnosis may involve enzyme activity assays in muscle, muscle biopsy, and genetic sequencing to identify pathogenic variants. Management focuses on minimizing exertional crises and optimizing energy availability through diet and tailored exercise programs; no specific cure exists as of current knowledge.

See also: enolase family, ENO1, ENO2, metabolic myopathies.