Control of Glycolysis

The rate of glycolysis changes in a particular cell from moment to moment as its energy 

A good illustration of how glycolytic flux can rapidly change is seen when yeast are grown under aerobic and anaerobic conditions with glucose as the carbon source. This effect, first observed by Louis Pasteur, is called the Pasteur effect and is depicted in Fig. 11-21. 

When grown under aerobic conditions, the yeast produces two ATP molecules from one molecule of glucose by substrate-level phosphorylation in glycolysis. The two molecules of pyruvate produced can then be completely oxidized to CO2, and each yields a further 15 molecules of ATP. This leads to a slow decrease in the concentration of glucose, a steady production of CO2, and relatively little change in the amount of ATP. Also, the two molecules of NADH can be reoxidized to NAD+ by the electron-transport system. (This produces yet more ATP, as discussed in Chap. 14.) 

When yeast are grown in an anaerobic environment, the utilization of glucose is markedly increased and the production of CO2 and ethanol rises dramatically with very little change in the concentration of ATP. While this phenomenon has been explained in many ways, the simplest requires the assumption that the yeast needs a constant amount of ATP for its energy requirements, irrespective of the conditions under which it is grown. 

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Ovadi, J. (1988). Old pathway—new concept Control of glycolysis by metabolite-modulated dynamic enzyme associations. Trends Biochem. Sci. 13,486-490. 

Figure 19-3. Control of glycolysis and gluconeoge-nesis in the liver by fructose 2,6-bisphosphate and the bifunctional enzyme PFK-2/F-2,6-Pase (6-phospho-fructo-2-kinase/fructose-2,6-bisphosphatase). (PFK-1, phosphofructokinase-1 [6-phosphofructo-1 -kinase] ...

Figure 3.9 Hormone and metabolite-mediated control of glycolysis...

Allosteric Enzymes Typically Exhibit a Sigmoidal Dependence on Substrate Concentration The Symmetry Model Provides a Useful Framework for Relating Conformational Transitions to Allosteric Activation or Inhibition Phosphofructokinase Allosteric Control of Glycolysis Is Consistent with the Symmetry Model Aspartate Carbamoyl Transferase Allosteric Control of Pyrimidine Biosynthesis Glycogen Phosphorylase Combined Control by Allosteric Effectors and Phosphorylation... 

Phosphofructokinase Allosteric Control of Glycolysis Is Consistent with the Symmetry Model... 

Fig. 12-5 Tile control of glycolysis by elevated concentrations of high-energy compounds within the mitochondria.

Much has been published on the controversial subject of the control of glycolysis. The following brief summary of some of the controls responsible for the Pasteur effect in yeasts is based mainly on a review by Sols and coworkers144 (see also, Fig. 7). (i) Isocitrate dehydrogenase (NAD ) (EC 1.1.1.41), one of the controlling enzymes of the tricarboxylic acid cycle (see Fig. 5), catalyzes the reaction... 

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.)...

Adenylate kinase, which is abundant in muscle as in many other tissues, decreases in dystrophic mouse and human muscle (H6, P7). This enzyme, by interconverting adenine nucleotides, probably functions in the control of glycolysis it seems reasonable to suppose, therefore, that its activity may be governed by the same factors which influence glycolytic enzymes, as discussed above. A severe decline in the activity of AMP deaminase occurs in muscular dystrophy (P6, P7) and also in denervated muscle (M12) and in some cases of muscle affected by hypokalemic periodic paralysis (E6). Skeletal muscle normally contains a higher concentration of this enzyme than other tissues in fact, it is almost absent from some, such as liver. Its physiological function, and hence the significance of the sharp decline in its activity in diseased muscle, is still a matter of speculation. 

What is the importance of the regulation of glycolysis Explain the role of allosteric enzymes in control of glycolysis. 

Hess, B. A. Boiteux. 1968b. Control of glycolysis. In Regulatory Functions of Biological Membranes. J. Jamefelt, ed. Elsevier, Amsterdam, pp. 148-62. 

Once again, the level of the cations is controlled by membrane processes and metabolism from bacteria to animals and plants so that the same dependences on cations are found in all forms of life. For example, intracellular control of glycolysis is partly through the magnesium and potassium concentrations. Here we observe, much as has been seen in the chemistry of zinc, iron, cobalt, and copper, that biology has few variants on particular systems but these systems are chosen with remarkable ingenuity. 

Pyruvate kinase is the enzyme that catalyzes this reaction. Like phospho-fructokinase, it is an allosteric enzyme consisting of four suhunits of two different types (M and L), as we saw with phosphofructokinase. Pyruvate kinase is inhibited hy ATP. The conversion of phosphoenolpyruvate to pyruvate slows down when the cell has a high concentration of ATP—that is to say, when the cell does not have a great need for energy in the form of ATP. Because of the different isozymes of pyruvate kinase found in liver versus muscle, the control of glycolysis is handled differently in these two tissues, which we will look at in detail in Chapter 18. 

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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