Enzymes of the Glycolytic Cycle

For over three decades the enzymes of the glycolytic cycle have been the subject of Augorous research by many investigators. Since much has been written concerning the details of the glycolytic reactions, this section 

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Figure 6.4 Glycolysis divided into five stages. It is not clear whether the reaction in which pyruvate is converted to acetyl-CoA, catalysed by pyruvate dehydrogenase, should be classified as a glycolytic enzyme or an enzyme of the Krebs cycle. Since the enzyme presents acetyl-CoA to the cycle, it is considered in this book as an enzyme of glycolysis (i.e. aerobic glycolysis).

As we look at some of the reactions of intermediary metabolism, we shall rationahze them in terms of the chemistry that is taking place. In general, we shall not consider here the involvement of the enzyme itself, the binding of substrates to the enzyme, or the role played by the enzyme s amino acid side-chains. In Chapter 13 we looked at specific examples where we know just how an enzyme is able to catalyse a reaction. Examples such as aldolase and those phosphate isomerase, enzymes of the glycolytic pathway, and citrate synthase from the Krebs cycle were considered in some detail. It may... 

When sodium fluoride is used alone for anticoagulation, three to five times greater concentrations than the usual 2 g/L are required. This high concentration and the inhibition of the glycolytic cycle are likely to cause fluid shifts and a change in the concentration of some analytes. Fluoride is also a potent inhibitor of many serum enzymes and in high concentrations also affects urease, used to measure urea nitrogen in many analytical systems. 

The sustained generation of energy from fat requires large supply of citric acid cycle intermediates. Recall that oxaloac-etate is derived from glucose via the enzymes of the glycolytic pathway and pyruvate carboxylase. 

The eleven constituent enzymes of the glycolytic system fall into the following categories dehydrogenases (2) phosphokinases (4) isomerases (4) and aldolase (1). The ratio of the number of dehydrogenases to the total number of enzymes is 2 11 in the glycolytic cycle and 5 12 in the citric-acid cycle. 

In all body fluids a relatively constant amount of cations and anions must be maintained by the cell for it to function normally. Since any disturbance in the ratio of ionic species in the tissue may stimulate profound changes, a consideration of these effects in terms of the known enzymes systems of the glycolytic cycle would be of considerable value. 

Methods for evaluating the status of enzymes in the glycolytic cycle in red cell hemolysates have been described using simple fluorescence spot tests which allow detection of enzyme defects in a group of enzymes, with determination of the speciflc defect deferred until later and applied only to those individuals found to be abnormal by the screening methods employed (Yunis, 1973). 

Cycles arise becanse both the glycolytic and gluconeogenic enzymes are simnltaneously active. Consequently, an increase in gluconeogenic flux can be achieved either by a decrease in the activity of the glycolytic enzyme(s) and/or an increase in the activity of the gluconeogenic enzyme(s). 

The enzyme phosphofructokinase is allosteric, that is, it is made up of equivalent units that possess specific reaction sites for the fixation of the substrate and product. Each unit exists in two conformational states one active with more affinity for the substrate, and one inactive. The reaction products of phosphofructokinase (FDP and ADP) displace the conformational equilibrium in favor of the active form of the enzyme. This may create a destabilizing effect on the excess entropy production. In the glycolytic cycle, the allosteric properties of the phosphofructokinase may lead to oscillations. Consider the following simple model... 

Flow of carbon atoms. What is the fate of the radioactive label when each of the following compounds is added to a cell extract containing the enzymes and cofactors of the glycolytic pathway, the citric acid cycle, and the pyruvate dehydrogenase complex (The label is printed in red.)... 

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