Isoform M1 of Pyruvate kinase PKM

Pyruvate kinase PKM isoform M1 (P14618-2) is a glycolytic enzyme that catalyzes the conversion of phosphoenolpyruvate to pyruvate in adult tissues. Unlike the fetal isoform M2, PKM M1 exhibits constitutively high pyruvate kinase activity independent of allosteric regulation by fructose 1,6-bisphosphate (UniProt: P14618-2). This metabolic distinction reflects the developmental switch from fetal to adult glycolytic regulation after birth.

PKM M1 is predominantly expressed in differentiated adult tissues where sustained, high-activity pyruvate kinase is required for efficient glucose metabolism. The protein functions as a central node in cellular energy production and has broader roles in biosynthetic pathways supporting macromolecule synthesis.

PKM M1 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls (mean log2 fold-change −0.30; Chaparral AD proteomics), based on quantitative proteomic analysis of post-mortem AD tissue across multiple subcellular fractions. This reduction may reflect impaired glycolytic capacity and energy metabolism dysfunction observed in AD neurodegeneration.