Adenosine monophosphate glycolysis

The reaction is essentially irreversible under physiological conditions and is a major regulatory step of glycolysis. PFK-1 is an inducible, highly regulated, allosteric enzyme. In its active form, muscle PFK-1 is a homotetramer (M.W. 320,000) that requires K+ or NH4, the latter of which lowers Km for both substrates. When adenosine triphosphate (ATP) levels are low during very active muscle contraction, PFK activity is modulated positively despite low concentration of fructose-6-phosphate. Allosteric activators of muscle PFK-1 include adenosine monophosphate (AMP), adenosine diphosphate (ADP), fructose-6-phosphate, and inorganic phosphate (Pi) inactivators are citrate, fatty acids, and ATP. 

For lipogenesis, glucose 6-phosphate is converted through glycolysis to pyruvate. Key enzymes that regulate this pathway in the liver are phosphofructokinase-1 (PFK-1) and pyruvate kinase. PFK-1 is aliosterically activated in the fed state by fructose 2,6-bisphosphate and adenosine monophosphate (AMP) (see Fig. 36.1). Phosphofructokinase-2, the enzyme that produces the activator fructose 2,6-bisphosphate, is dephosphorylated and active after a meal (see Chapter 22). Pyruvate kinase is also activated by dephosphorylation, which is stimulated by the increase of the insulin/glucagon ratio in the fed state (see Fig. 36.1). 

Phosphofructokinase 2 (PFK-2) is negatively regulated by phosphorylation in the liver (the enzyme that catalyzes the phosphorylation is the cyclic adenosine monophosphate [cAMP]-dependent protein kinase). However, in skeletal muscle, PFK-2 is not regulated by phosphorylation. This is because the skeletal muscle isozyme of PFK-2 lacks the regulatory serine residue, which is phosphorylated in the liver. However, the cardiac isozyme of PFK-2 is phosphorylated and activated by a kinase cascade initiated by insulin. This allows the heart to activate glycolysis and to use blood glucose when blood glucose levels are elevated. 

Phosphofructokinase (EC 2.7.1.30) catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate as the key regulatory enzyme of glycolysis. Inhibition of phosphofructokinase by adenosine triphosphate and its activation by adenosine monophosphate and inorganic phosphate is held responsible for the induction of the Pasteur effect (for review see Ramaiah 1974). 

The two major metabolic pathways necessary for normal RBC metabolism are the hexose monophosphate shunt pathway, with its associated enzyme systems, and the Embden-Myerhof pathway of anaerobic glycolysis. The former is responsible primarily for maintaining Hgb in the rednced state and thns preventing the formation of methemoglobin, while the latter metabolizes glucose to lactic acid, which leads to adenosine triphosphate formation. 

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