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Example Question #1 : Gluconeogenesis Energetics
In order for gluconeogenesis to generate one molecule of glucose, how many molecules of ATP and/or GTP are needed?
Answering this question requires knowledge of the pathway of gluconeogenesis. In this pathway, non-carbohydrate carbon substrates such as lactate, pyruvate, and certain amino acids are used to generate glucose as the final product. Much of this pathway utilizes the same enzymes used in glycolysis, which is essentially the reverse of gluconeogenesis. However, it is critical to note that there are 3 reactions in glycolysis that are irreversible. Therefore, gluconeogenesis is not an exact reverse of glycolysis, and instead there are a few different enzymes in gluconeogenesis that bypass these irreversible reactions. One of the irreversible steps in glycolysis is the formation of pyruvate from phosphoenolpyruvate (PEP), catalyzed by the glycolytic enzyme pyruvate kinase. To bypass this irreversible reaction, gluconeogenesis makes use of two enzymes. First, the enzyme pyruvate carboxylase converts pyruvate into oxaloacetate, which requires the input of one molecule of ATP per molecule of pyruvate used. Next, the gluconeogenic enzyme PEP carboxykinase converts oxaloacetate into PEP, using one molecule of GTP per molecule of oxaloacetate used. The other step that requires an investment of energy is by a reaction that is reversible. The conversion of 3-phosphoglycerate into 1,3-bisphosphoglycerate (1,3-BPG) by the enzyme phosphoglycerate kinase utilizes one molecule of ATP per molecule of 1,3-BPG generated. This is a reversible reaction. Now, we can add up the energy requirements. Since each of these reactions need to occur twice in order to generate a single molecule of glucose, we'll need to multiply the energy investment by two in each step. Thus, we have two molecules of ATP from the reaction catalyzed by pyruvate carboxylase. We also have two molecules of GTP from the reaction catalyzed by PEP carboxykinase. And lastly, we have two molecules of ATP used from the reaction catalyzed by phosphoglycerate kinase. Adding all of these up, we have a total of four molecules of ATP and two molecules of GTP.