Reversal of Glycolysis

3 and 4 of the glucose unit. Since the same isotope distribution would be 

These results can best be depicted in the scheme presented by Wood  

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Thermodynamic Barriers Prevent a Simple Reversal of Glycolysis... 

Three nonequilibrium reactions catalyzed by hexoki-nase, phosphofructokinase, and pyruvate kinase prevent simple reversal of glycolysis for glucose synthesis (Chapter 17). They are circumvented as follows ... 

The convetsion of fructose 1,6-bisphosphate to fructose 6-phosphate, to achieve a reversal of glycolysis, is catalyzed by fructose-l,6-bi pho pbatase. Its ptesence determines whether or not a tissue is capable of synthesizing glycogen not only from pymvate but also from ttiosephosphates. It is present in hvet, kidney, and skeletal muscle but is probably absent from heart and smooth muscle. 

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. 

GlUCOneogenesis This pathway produces glucose from carbon-containing molecules that are not carbohydrates. For example, it can convert pyruvate into glucose, the reverse of glycolysis. 

Much of the glyceraldehyde 3-phosphate produced by the Calvin cycle in chloroplasts is exported to the cytosol and used to produce the disaccharide, sucrose. First the glyceraldehyde 3-phosphate is converted to fructose 6-phos-phate and glucose 1-phosphate. The chemical reactions involved are essentially a reversal of glycolysis (see Topic J3). The glucose 1-phosphate is then converted to UDP-glucose and this reacts with fructose 6-phosphate to synthesize sucrose 6-phosphate ... 

Relationship between Gluconeogenesis and Glycolysis Why is it important that gluconeogenesis is not the exact reversal of glycolysis ... 

The phosphoenolpyruvate may then transport out of the mitochondria and yield glucose by the reversal of glycolysis, with the exception of the PFK I and... 

Figure 2.5 Gluconeogenesis is the reversal of glycolysis, attained through the use of four unique enzymes glucose-6-phosphatase (A), fructose-1,6-bisphosphatase (5), PEP carboxykinase (6) and pyruvate carboxylase (7). Although phosphoglycerate kinase is shared with glycolysis, in gluconeogenesis this reaction requires the input of ATP.

The further metabolism of pyruvate or PEP is still under investigation. Increasing support is available for the view that the C3 residue from decarboxylation is converted, by a reversal of glycolysis, into a storage carbohydrate which later serves... 

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. 

Gluconeogenesis involves several enzymatic steps that do not occur in glycolysis thus glucose is not generated by a simple reversal of glycolysis. 

Gluconeogenesis from pyruvate is essentially the reverse of glycolysis, with the exception of three nonequilibrium reactions (Figure 15-1). These reactions are... 

Phosphoenolpyruvate is converted to fructose-1,6-bisphosphate by reversal of glycolysis in the cytosol via reactions that are at near-equilibrium and whose direction is dictated by substrate concentration. Conversion of fructose-1,6-bisphosphate to fructose-6-phosphate is a nonequilibrium step, catalyzed by fructose-1,6-bisphosphatase ... 

In glycolysis, glucose is converted into pyruvate in gluconeogenesis, pyruvate is converted into glucose. However, gluconeogenesis is not a reversal of glycolysis. Several reactions must differ because the equilibrium of glycolysis lies far on the side of pyruvate formation. The actual AG for the formation... 

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. 

Gluconeogenesis, the synthesis of new glucose molecules from noncarbohydrate precursors, occurs primarily in the liver. The reaction sequence is the reverse of glycolysis except for three reactions that bypass irreversible steps in glycolysis. 

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