Work

Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease

Year: 2026

Type: review

Abstract: As a bifunctional enzyme, phosphofructokinase-2/fructose 2,6-bisphosphatase (PFKFB or PFK-2) produces and degrades fructose 2,6 bisphosphate (Fru-2,6-P 2 ). Because Fru-2,6-P 2 is a strong allosteric activator of glycolysis, PFKFB is critical to glycolytic regulation. Four isoenzymes of PFKFB have been identified (PFKFB1-4). PFKFB2 is considered the cardiac isoenzyme and is distinct among the isoforms because of its complex regulation via multi-site phosphorylation. It plays critical roles in cardiac physiological responses to stress, with its loss a key driver of pathophysiology in metabolic cardiac diseases. However, PFKFB2 is also expressed in multiple additional tissues, and is involved with non-cardiac pathologies including cancer. Therefore, an ongoing area of research is the regulation of PFKFB2 activity and abundance. Here, we review the history and present knowledge of the structure, function, tissue distribution, and roles of PFKFB2 in physiology, stress response, and pathophysiology, both in the heart and other tissues systemically.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2026.113294

Authors: Kylene M. Harold, Wan Hee Yoon, Kenneth M. Humphries

Institutions: Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center

Language: English

Topic: Metabolism, Diabetes, and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430