Control points, of glycolysis

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.

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. 

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... 

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. 

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. 

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. 

Kidney medulla From the metabolic point of view the kidney is virtually two organs, the cortex and the medulla. The cortex contains the glomeruli, through which the blood is filtered, the proximal tubules and part of the distal tubules, from which ions and molecules are reabsorbed. The cortex is well supplied with blood so that ATP is generated by the oxidation of fuels. The medulla is metabolically quite different. Here the ATP is required for the reabsorption of ions from the loop of Henle. Some ATP is generated by anaerobic glycolysis, since the supply of blood, and therefore of oxygen, to the medulla is much poorer than to the cortex. This reflects control of the uptake of water and Na+ ions into the blood by the counter current mechanism. This depends on a slow flow of the blood in the capillaries. 

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. 

Question Which enzyme is the main point of control of glycolysis ... 

Fig. 7.-The Control of Glycolysis (after Cohen874). (Points of inhibition are indicated by black arrows, and of activation by dotted arrows. Published by permission of the copyright owners.)...

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. 

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. 

Indeed it appears that PPj-PFK is not a point of control for glycolysis in these anaerobic organisms and is not affected by concentrations of ATP/ADP/AMP which are key controllers of mammalian PFK. Nor is the main effector molecule of mammalian PFK, fructose-2,6-bisphosphate, active in this way in these anaerobic organisms. 

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. 

Control of glycolysis. The metabolites and enzymes are denoted bytheirstandard abbreviations (see Fig. 10-8 forthe full names). The dashed arrows specify regulation of the enzymes to which they point, and the -i- and - signs denote activation and inhibition, respectively. 

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