B) Three strongly exergonic, non-equilibrium reactions
Explanation:
Glycolysis is regulated primarily by three strongly exergonic, non-equilibrium reactions.
These reactions happen as follows:
The initial step in using glucose in glycolysis is its ATP phosphorylation to provide glucose-6-phosphate, this reaction is irreversible under intracellular conditions and is catalyzed by hexokinase. The hexokinase reaction utilizes a high-energy ATP bond and forms a low-energy compound, which is glucose-6-phosphate. Because of its inhibition by the product, hexokinase ceases to function as soon as a significant amount of glucose-6-phosphate is produced and remains inactive until the level of this molecule decreases as a result of its use by other reactions. It can be inferred that hexokinase is a regulatory enzyme in which glucose-6-phosphate is both the substrate and the allosteric regulator.
Phosphofructokinase is an important site of metabolic regulation because the activity of this enzyme can be increased or decreased by a number of common metabolites. These effects are allosteric, as they are the result of an interaction between the metabolite and the protein catalyst at a different site from that where catalysis occurs. The enzyme requires Mg2 + and is specific for fructose-6-phosphate. Its activity is stimulated by ADP and when there is excess ATP it is inhibited. In addition to ATP, citrate and isocitrate may act as inhibitory modulators of phosphofrutokinase, thus acting as negative effectors. On the other hand, AMP, ADP and fructose-6-phosphate stimulate the enzyme, playing the role of positive effectors. When the ATP / ADP ratio is high, phosphofrutokinase enzyme activity is severely inhibited, however when this same ratio is low, phosphofrutokinase activity is accelerated. Since under aerobic conditions the ATP / ADP ratio is high, the speed of the phosphofrutokinase reaction is reduced and consequently glycolysis is also reduced. Depending on the level of Acetyl CoA, the level of Krebs cycle intermediates may increase. Therefore, allosteric inhibition of phosphofructokinase, mainly by ATP, is the main regulating mechanism of glycolysis.
The pyruvate kinase reaction is a secondary control point in glycolysis. It is also an allosteric enzyme. At high ATP concentrations, the apparent affinity of pyruvate kinase for phosphoenolpyruvate is relatively low and the reaction rate will be equally low at normal phosphoenolpyruvate concentrations. Pyruvate kinase is also inhibited by Acetyl CoA and long chain fatty acids, both important fuels of the Krebs Cycle. Thus, whenever the cell already has a high ATP concentration, glycolysis is inhibited by the action of phosphofrutokinase or pyruvate kinase. On the other hand, at low ATP concentrations, the apparent affinity of pyruvate kinase for phosphoenolpyruvate increases, this behavior enables the enzyme to transfer the phosphoenolpyruvate phosphate group to ADP.
