PKM1

PKM1 (pyruvate kinase muscle isoform 1) is a glycolytic enzyme that catalyzes the final step of glycolysis, converting phosphoenolpyruvate to pyruvate and generating ATP, thereby supporting efficient cellular energy production in tissues with high energetic demand such as heart, brain, and skeletal muscle^[1][2]. Alternative splicing of the PKM gene produces the closely related PKM1 and PKM2 isoforms, with PKM1 containing exon 9 and PKM2 containing exon 10^[2][3]. Mechanistically, PKM1 is constitutively active and predominantly exists as a highly active tetramer, promoting glycolytic flux toward ATP generation, whereas PKM2 displays more complex allosteric regulation and can support anabolic metabolism in proliferating cells^[2][3][4]. Therefore, PKM1 is closely associated with metabolic programs that favor oxidative energy production rather than biomass accumulation^[3][4]. In disease models, PKM1 has emerged as an important regulator of cardiac metabolic adaptation under hemodynamic stress, where it is required for augmentation of glycolytic flux, mitochondrial respiration, ATP production, and pyruvate dehydrogenase complex activity^[1]. Cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis, whereas inducible PKM1 overexpression protects against pressure overload-induced cardiomyopathy and heart failure^[1]. Compared with PKM2, increased PKM1 expression has also been associated with suppression of prostate tumor progression in experimental models, highlighting distinct isoform-dependent effects on cellular metabolism and disease phenotypes^[4][5]. For experimental applications, pharmacological pyruvate kinase activators that promote a PKM1-like high-activity state have been used to investigate metabolic regulation and tumor suppression mechanisms^[5].