Control Points in Glycolysis and the Committed Step
Several far-from-equilibrium glycolytic reactions are common regulatory sites. PFK-1 responds to ATP, AMP and citrate and catalyses the committed step. Control of pathway flux can be distributed across enzymes and depends on cellular conditions.
What a learner can do afterwards
- Names the three common far-from-equilibrium glycolytic reactions and explains why PFK-1 catalyses the committed step.
- Predicts PFK-1 responses to inhibitory ATP, AMP and citrate under stated conditions.
- Uses stated perturbation results to compare flux control without inferring it from equilibrium status alone.
1 · Read
Mammalian glycolysis has three common far-from-equilibrium reactions: glucose phosphorylation by hexokinase or glucokinase; fructose-6-phosphate phosphorylation by PFK-1; and conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase. Strongly negative delta G under cell conditions makes direct reversal negligible. Many remaining reactions are closer to equilibrium and can reverse as concentrations change.
PFK-1 is phosphofructokinase-1. It converts fructose-6-phosphate to fructose-1,6-bisphosphate using ATP. This is the committed glycolytic step because earlier glucose-6-phosphate can enter other pathways, such as glycogen production or the pentose phosphate pathway. Commitment concerns pathway entry after those branches, not exclusive ownership of flux control.
ATP is a PFK-1 substrate, but at high concentrations it can also inhibit the enzyme allosterically. AMP can activate PFK-1 as energy demand rises. Citrate can inhibit it too. Citrate abundance may reflect metabolic supply and demand, but does not uniquely prove that a downstream pathway is full. Predict direct enzyme effects with other conditions stated.
Flux control can be shared among enzymes and depends on conditions. Near-equilibrium status alone does not predict the effect of inhibition. To compare targets, apply the same activity reduction to each under the same conditions and measure steady-state pathway flux. A larger measured flux decrease indicates a stronger effect for that tested perturbation, not a universal best target.
PFK-1 catalyses glycolysis's committed step and responds to energy-related signals. Common regulatory reactions do not alone determine all pathway flux control.
Lesson, questions and flashcards written for this dataset.
Readings and flashcards written for this dataset.
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