Glycolysis hexokinase control

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.

These considerations do not take into account the major glycolytic controls exerted by the hexokinase-phosphofructokinase system (230) but they do show that G-3PDH could act as a regulatory enzyme in response to the NAD+ NADH and ATP ADP X Pi ratios in the cell. These ratios in conjunction with appropriate substrate (i.e., G-3P, DPGA, and Pi) concentrations prime the enzyme for glycolysis or gluconeogenesis in accord with the particular environment and needs of the cell. 

Glycolysis is tightly regulated in coordination with other energy-yielding pathways to assure a steady supply of ATP. Hexokinase, PFK-1, and pyruvate kinase are all subject to allosteric regulation that controls the flow of carbon through the pathway and maintains constant levels of metabolic intermediates. 

When real data from the experiment on glycolysis in a rat liver extract (Fig. 15-33) were subjected to this kind of analysis, investigators found flux control coefficients (for enzymes at the concentrations found in the extract) of 0.79 for hexokinase, 0.21 for PFK-1, and 0.0 for phosphohexose isomerase. It is not just fortuitous that these values add up to 1.0 we can show that for any complete pathway, the sum of the flux control coefficients must equal unity. 

Substrate level control - In this control mechanism, high levels of the product of a reaction inhibit the ability of the small amounts of substrate present to react. An example is the first step in glycolysis, catalyzed by hexokinase. It is inhibited by the product of its action, glucose-6-phosphate. If glycolysis is blocked for any reason, glucose-6-phosphate accumulates. 

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. 

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