Glycolysis control points

Figure 5.3 Major control points of glycolysis and the TCA cycle. Enzymes I, hexokinase II, phosphofructokinase III, pyruvate kinase IV, pyruvate dehydrogenase V, citrate synthase VI, aconitase VII, isocitrate dehydrogenase VIII, a-oxoglutarate dehydrogenase.

Feed-forward control is more likely to be focused on a reaction occurring at or near the end of a pathway. Compounds produced early in the pathway act to enhance the activity of the control enzyme and so prevent a back log of accumulated intermediates just before the control point. An example of feed-forward control is the action of glucose-6-phosphate, fructose-1,6-bisphosphate (F-l,6bisP) and phosphoenol pyruvate (PEP), all of which activate the enzyme pyruvate kinase in glycolysis in the liver. 

The interconversion of fructose-6-phosphate and fructose-1,6 bis phosphate is a control point in glycolysis and gluconeogenesis. Gluconeogenesis is a pathway which allows carbon atoms from substrates such as lactate, glycerol and some amino acids to be used for the synthesis of glucose, so it is in effect physiologically the opposite of... 

Phiosphoffuctokinases (PFK-1 and PFK-2) PFK-1 is the rate-limiting enzyme and main control point in glycolysis. In this reaction, fructose 6-phosphate is phosphorylated to fructose 1,6-bisphosphate using ATP. 

The irreversible phosphorylation reaction catalyzed by phospho fructokinase-1 (PFK-1) is the most important control point and the rate-limiting step of glycolysis (Figure 8.16). PFK-1 is controlled by the available concentrations of the substrates ATP and fructose 6 phosphate, and by regulatory substances described below. 

Step 3 is the second control point of glycolysis and involves the conversion of fructose 6-phosphaie into fructose 1,6-bisphosphate, catalyzed by phosphofructokinase. 

In glycolysis each glucose molecule is converted into two pyruvate molecules. In addition, two molecules each of ATP and NADH are produced. Reactions with double arrows are reversible reactions and those with single allows are irreversible reactions that serve as control points in the pathway. 

This reaction is one of two substrate level phosphorylations in glycolysis (the other is catalyzed by phosphoglycerate kinase). The enzyme is a key control point for glycolysis. 

PFK (also called PFK-1) is an enzyme of glycolysis that is a critical control point regulating the pathway. It catalyzes the conversion of fmctose-6-phosphate (F6P) to fructose-1,6-bisphosphate (F1,6BP) by adding a phosphate from ATP, creating ADP. 

Phosphofructokinase (PFK) is a major control point for glycolysis. PFK is allosterically inhibited by ATP and citrate, allosterically activated by AMP, ADP, and F2,6BP. Thus, carbon movement through glycolysis is inhibited at PFK when the cell contains ample stores of ATP and oxidizable substrates. Additionally, PFK is activated by AMP and ADP because they indicate low levels of ATP in the cell. F2,6BP is the major activator, though, because it reciprocally inhibits fructose 1,6 bisphosphatase, which is the gluconeogenic enzyme that catalyzes the reversal of this step. 

Gluconeogenesis and glycolysis are reciprocally regulated so that one pathway is relatively inactive while the other is highly active. Phosphofructokinase and fructose 1,6-bisphosphatase are key control points. 

Recall Which reactions are the control points in glycolysis ... 

The final step of glycolysis is also a major control point in glucose metabolism. Pyruvate kinase (PK) is allostericaUy affected by several compounds. ATP and alanine both inhibit it. The ATP makes sense because there would be no reason to sacrifice glucose to make more energy if there is ample ATP. The alanine may be less intuitive. Alanine is the amino version of pyruvate. In other words, it is one reaction away from pyruvate via an enzyme called a transaminase. Therefore, a... 

Hexokinase and pyruvate kinase, the enzymes that catalyze the first and last steps, respectively, in glycolysis are also important control points. They have the effect of slowing down the pathway when energy is not needed and speeding it up when there is a need. 

The control points in glycolysis are the reactions catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase. 

The third control point is the last step of glycolysis, the conversion of phosphoenolpyru-vate to pyruvate catalyzed by pyruvate kinase. This enzyme, too, is an allosteric enzyme that is inhibited by higher concentrations of ATP. 

What is the third control point in glycolysis How is it responsive to cellular needs ... 

The third control point is in the last step of glycolysis. The enzyme for this step, pyruvate kinase, is inhibited by a high ATP concentration. If the cell does not need ATP, the ATP concentration will inhibit glycolysis and slow the production of ATP. As the need for ATP increases, the inhibition of the enzyme no longer occurs and glycolysis proceeds to make more ATP. 

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