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The fructose 2,6‐bisphosphate cycle bioswitch and metabolic coordination
Author(s) -
Okar David Anthony
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.658.5
Subject(s) - fructose 2,6 bisphosphate , glycolysis , fructose , metabolism , carbohydrate metabolism , fructose 1,6 bisphosphatase , microbiology and biotechnology , metabolic pathway , chemistry , biochemistry , biology , phosphofructokinase
Objective Provide a comprehensive mechanistic description of metabolic regulation that can account for the full spectrum of positive synergistic effects observed while investigating the modulation of hepatic glycolysis as a therapy for diabetes‐associated hyperglycemia. Method Search pertinent literature for examples of metabolic coordination including those observed for hepatic fructose 2,6‐bisphosphate (F‐2,6‐P2 and 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase (PFK‐2/FBP‐2) and identify common elements, thereby highlighting mechanisms that coordinate metabolism within the liver and in relation to fuel homeostasis. Results The most obvious regulatory elements common to metabolic coordination are chemical cycles, protein:protein interactions, and translocation between sub‐cellular locations. All of these constitute biological switches and some coordinate across levels of biological organization. Conclusions The PFK‐2/FBP‐2 dimer is a bioswitch that along with F‐2,6‐P2 primarily modulates the committing step to glycolysis and coordinately regulates multiple aspects of fuel metabolism at the molecular, cellular, tissue/organ, and systemic levels of biological organization. Funding: VA.