F26BP enables control of glycolysis rate independent of energy state.

ABSTRACT: Glycolysis is a conserved metabolic pathway that produces ATP and biosynthetic precursors. Multiple allosteric regulators control glycolytic enzymes in vitro. For example, phosphofructokinase (PFK) is allosterically regulated by fructose-2,6-bisphosphate (F26BP), ATP, ADP, AMP, citrate, acyl-CoA, and inorganic phosphate. It is not well understood which properties of homeostasis are enabled by each of these regulators, and whether they perform redundant or distinct functions. Using mathematical modeling and experiments with human cells lacking F26BP, we demonstrate that F26BP alters glycolytic rate independent of cellular ATP demand-a unique function not shared by other regulators. We also identified several downstream glycolytic intermediates as novel regulators of F26BP levels. Our

SUBMITTER: Kober MM 

PROVIDER: S-EPMC12873801 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature