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Glycolysis is regulated at its 3 irreversible steps (hexokinase, PFK-1, pyruvate kinase) differently in muscle and liver: In muscle, regulation is based on energy charge (ATP/AMP ratio) to supply ATP for contraction — PFK-1 is the main control point inhibited by ATP and low pH and activated by AMP during high activity, hexokinase is inhibited by glucose-6- phosphate, and pyruvate kinase is inhibited by ATP/alanine and activated by fructose-1,6-bisphosphate. In liver, regulation maintains blood glucose — PFK-1 is less sensitive to ATP but inhibited by citrate and potently activated by fructose-2,6- bisphosphate (which rises when glucose is high), and glucokinase (hexokinase IV) has low affinity for glucose, is not inhibited by glucose-6-phosphate, and only works when glucose is abundant to favor storage.
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