Phosphofructokinase
PHOSPHOFRUCTOKINASE-1 (PFK-1)
- Catalyzes rate-limiting step in glycolysis
- Catalyzes irreversible phosphorylation of F6P to F1,6P.
- Allosterically regulated (hormonally regulated in liver)
- Citrate, intermediate of citric acid cycle
- ATP, final product of glycolysis and cellular respiration
- H+, symptom of lactic acid buildup in exercising muscle
- AMP, marker of ATP depletion.
- Fructose-2,6-bisphosphate (special case)
- PFK-2: F6P --> F2,6P (activates PFK-1)
- FBP-2 (fructose-2,6-bisphosphatase): F2,6P --> F6P (deactivates PFK-1)
- PFK-2/FBP-2 regulated differently in different tissues
Skeletal muscle
- Feed-forward activation
- Substrate-level regulation: F6P
- When F6P HIGH: FBP-2 inactive and PFK-2 active (activate PFK-1)
- When F6P LOW: FBP-2 active and PFK-2 inactive (inhibits PFK-1 activity)
Liver
- Hormonal regulation: PFK-2 has phosphorylation site (unlike muscle)
- PFK-2 is INACTIVE when phosphorylated
- Glucagon activates protein kinase A (PKA), which phosphorylates PFK-2
- Insulin activates phosphoprotein phosphatase (PPP), which dephosphorylates PFK-2
- HIGH blood glucose
- INSULIN secreted --> PPP activated --> PFK-2 dephosphorylated (ACTIVE)
- HIGH F2,6P activates PFK-1
- Promotes glycolysis
- LOW blood glucose
- GLUCAGON secreted --> PKA activated --> PFK-2 phosphorylated (INACTIVE)
- LOW F2,6P deactivates PFK-1
- NO glycolysis
Liver responds to entire body's glucose needs
- Site of gluconeogenesis: glucose synthesized from non-carbohydrate precursors and released into the bloodstream