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Suraj Prakash Sharma | Ekta Chotia



AMP-activated protein kinase (AMPK) is an enzyme that plays a central role in energy metabolism. AMP is activated when the cell has high AMP:ATP ratio. AMPK is involved in lipid and glucose metabolism. Once activated phosphorylates target proteins (enzymes and transcription factors). AMPK switches off anabolic pathways (e.g., protein and lipid synthesis) and switches on catabolic pathways (e.g., glycolysis and fatty acid oxidation). AMPK promotes glycolysis in cardiac and skeletal muscle during exercise. It increase the number of glucose transporters to the plasma membrane. In cardiac cells, AMPK stimulates glycolysis by activating PFK-2.

11.5.      Pyruvate kinase

Pyruvate kinase is the third regulated enzyme of glycolysis. Pyruvate kinase  is regulated by various allosteric effectors like AMP, ATP and Acetyl –CoA. A high AMP concentration (an indicator of low energy production) activates pyruvate kinase. In contrast, pyruvate kinase is inhibited by a high ATP concentration (an indicator that the cell’s energy requirements are being met). Acetyl-CoA, which accumulates when ATP is in rich supply, inhibits pyruvate kinase.

F-1,6-BP activates the  Pyruvate kinase  in the liver, a second example of feed forward stimulation. Alanine (a biosynthetic product of pyruvate) is an allosteric inhibitor of pyruvate kinase. Phosphorylation of pyruvate kinase is regulated by blood glucose level, just like PFK. High glucagon (low blood sugar) causes phosphorylation, which in this case renders the enzyme inactive.

11.6.      Hemolytic Anemia

Pyruvate kinase deficiency causes hemolytic anemia, since red blood cells depend entirely on glycolysis for ATP synthesis. Pyruvate kinase deficiency causes accumulation of 1,3 BPG and PEP. The concentration  of pyruvate and lactate are lower than normal in this disorder.

Acetyl CoA is an allosteric effector of both glycolysis and gluconeogenesis. Acetyl-CoA inhibits pyruvate kinase and reciprocally activates pyruvate carboxylase. Acetyl CoA also inactivates pyruvate dehydrogenase providing a regulatory link between glycolysis and the citric acid cycle. High concentrations of acetyl-CoA are indicative of high energy supplies. When the energy supply is high, metabolites are directed towards storage in the form of glycogen.

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