Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Biosynthesis of Carbohydrates in Animal Tissues
Gluconeogenesis requires a significant energy input

Table 20-1 lists the reactions leading from Pyruvate to Blood glucose. The overall reaction is as follows:

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Table 20-1. Sequential reactions of Gluconeogenesis leading from pyruvate to glucose¹⁾

¹⁾ Bypass reactions are highlighted in red; all other reactions represent the Reversal of the corresponding steps in The Glycolytic Pathway. The numbers on the right indicate that a given reaction must occur twice because The formation of a single glucose molecule requires two three-carbon precursors.

For each molecule of glucose synthesized from pyruvate, six high-energy phosphate groups are consumed—four from ATP and two from GTP. In addition, two molecules of NADH are required for the reductive steps. Clearly, this equation is not a simple reversal of the equation describing The conversion of glucose to pyruvate during Glycolysis, since that conversion yields a net total of only two molecules of ATP.

Thus, the Synthesis of glucose from pyruvate is quite costly for the Organism. However, a significant portion of this metabolic cost serves merely to ensure the irreversibility of gluconeogenesis. Under intracellular conditions where the value of ∆G_P for ATP can reach 16 kcal/mol (Section 14.10), the overall standard free-energy change for glycolysis is at least —15 kcal/mol. Under the same conditions, the overall free-energy change for gluconeogenesis (the synthesis of glucose from pyruvate) is substantially greater in magnitude. Consequently, under normal intracellular conditions, both glycolysis and gluconeogenesis proceed as essentially irreversible processes.