Phosphoglycerate mutase 1 (PGAM1)

Phosphoglycerate mutase 1 (PGAM1) is a critical glycolytic enzyme that catalyzes the reversible interconversion between 3-phosphoglycerate and 2-phosphoglycerate, an essential step in glycolysis and gluconeogenesis[3][4][1]. PGAM1 requires 2,3-bisphosphoglycerate as a cofactor and is chiefly found in the cytoplasm of diverse non-muscle tissues[2][4]. It has a pivotal role in metabolic regulation, influencing not only energy production but also biosynthetic pathways such as serine synthesis and the pentose phosphate pathway[1][2]. Overexpression and dysregulation of PGAM1 are frequently observed in various cancers, correlating with enhanced cell proliferation, invasiveness, and poor patient prognosis, making it an emerging therapeutic target in oncology[1][2]. While several small molecule inhibitors (e.g., PGMI-004A) have demonstrated anti-tumor potential by impairing cancer cell metabolism, clinical translation requires careful consideration of metabolic safety and tissue specificity[2].

Other names

Phosphoglycerate mutase 1PGAM1PGAMAPGAM-BBPG-dependent PGAM 1Phosphoglycerate mutase isozyme BPhosphoglycerate mutase A (nonmuscle form)HEL-S-35, epididymis secretory protein Li 35phosphoglycerate mutase 1 (brain)

Inhibition of glycolytic activity via catalysis blockade (shRNA or small molecule inhibition decreases cell proliferation and tumor growth)[1][2] PGAM1 inhibition leads to altered metabolic flux in glycolysis and pentose phosphate pathways, affecting nucleotide biosynthesis and redox balance[2] Targeting phosphorylation or protein-protein interaction sites to suppress its activity in cancers[2]