Gluconeogenesis energetics

Mechanism for Gluconeogenesis. Since the glycolysis involves three energetically irreversible steps at the pyruvate kinase, phosphofructokinase, and hexokinase levels, the production of glucose from simple noncarbohydrate materials, for example, pyruvate or lactate, by a reversal of glycolysis ( from bottom upwards ) is impossible. Therefore, indirect reaction routes are to be sought for. 

Seven glycolytic reactions are reversible and are used in the synthesis of glucose from lactate or pyruvate. However, three of the reactions are irreversible and must be circumvented by four alternate reactions that energetically favor the synthesis of glucose. These reactions, unique to gluconeogenesis, are described below. 

Hydrolysis of fructose 1,6-bisphosphate by fructose 1,6-bispho -phatase bypasses the irreversible phosphofructokinase-1 reaction, and provides an energetically favorable pathway for the formation of fructose 6-phosphate (Figure 10.4). This reaction is an important regulatory site of gluconeogenesis. 

How is it possible that both the glycolytic degradation of glucose to lactate and the reverse process, formation of glucose from lactate (gluconeogenesis), are energetically favorable ... 

The second section of the book is Fuel Metabolism and Energetics. Important pathways and enzymes involved in fuel utilization are discussed in the chapters Pyruvate Dehydrogenase Complex Deficiency Mitochondrial En-cephalomyopathy, and Systemic Carnitine Deficiency. The role of gluconeogenesis in glucose homeostasis is illustrated by a discussion in the chapter Neonatal Hypoglycemia. 

Conceptual Insights, Energetics of Glucose Metabolism. See the section on gluconeogenesis in the Conceptual Insights module to review why and how gluconeogenesis must differ from the reversal of glycolysis. 

As we have seen in glycolysis and gluconeogenesis, biosynthetic and degradative pathways rarely operate by precisely the same reactions in the forward and reverse directions. Glycogen metabolism provided the first known example of this important principle. Separate pathways afford much greater flexibility, both in energetics and in control. 

Decarboxylation drives the condensation of malonyl ACP and acetyl ACP. In contrast, the condensation of two molecules of acetyl ACP is energetically unfavorable. In gluconeogenesis, decarboxylation drives the formation of phosphoenolpyruvate from oxaloacetate. 

The formation of glucose from pyruvate is energetically unfavorable unless it is coupled to reactions that are favorable. Compare the stoichiometry of gluconeogenesis with that of the reverse of glycolysis. 

The input of four additional high-phosphoryl-transfer-potential molecules in gluconeogenesis changes the equilibrium constant by a factor of 10, which makes the conversion of pyruvate into glucose thermodynamically feasible. Without this energetic input, gluconeogenesis would not take place. 

FERMENTATION AN ANCIENT HERITAGE The Energetics of Glycolysis Regulation of Glycolysis GLUCONEOGENESIS... 

This step is bypassed in gluconeogenesis because it is highly unfavorable energetically. 

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