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The role of glucose-6-po4 (g6p) as a central metabolite in various biochemical pathways, including glycolysis, glycogen synthesis, gluconeogenesis, and the pentose phosphate pathway. The enzymes involved in the formation and utilization of g6p, as well as the energy requirements and irreversibility of certain reactions.
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Talk about a traffic jam, glucose-6-PO 4 (G6P) is at the crossroads of at least 4 biochemical pathways ( click 1 ). Converting G6P to fructose-6-PO 4 commits the molecule to glycolysis ( click 1 ). On the other hand G6P can enter the glycogen synthesis pathway by being converted to glucose-1-PO 4 ( click 1 ). In liver G6P is the source of blood glucose ( click 1 ). Finally, by an oxidation reaction G6P is converted into 6-phosphoglucono-d-lactone and enters the pentose phosphate pathway ( click 1 ). The steady-state concentration of G6P depends on all these reactions plus those that form G6P. Click 1 to go on.
Finally, we must decide why some reactions of glucose-6-PO 4 are not reversible ( click 1 ). The answer will be found in the DGo' for the reaction. Recall, a large negative DGo' indicates the forward direction is favored. To reverse the reaction an equivalent amount of energy must be available. For example, when ATP is hydrolyzed to ADP
1. Glucose-6-PO 4 is clearly a molecule that has many metabolic fates. Can you think of a molecule in glycolysis that has only one? (click 1 for answer)
Glucose. Glucose has only one fate and that is to be converted into glucose-6-PO 4. One must consider, however, that glucose is generally found outside the cell, blood glucose, for example.
2. How much energy is required to reverse the glucose-6-phosphatase reaction?
A phosphate group must bind directly to the -OH group in the 6th position on the glucose molecule, replacing a water molecule. The energy requirement of that reaction is DGo’=13.8 kJ/mol
3. Is the phosphorylation of glucose by ATP an anabolic or catabolic reaction?
Catabolic. It catabolic because it results in the release of a substantial amount of free energy, i.e., exergonic. Similarly, the reaction takes place in a catabolic pathway. But, one could also argue that ATP hydrolysis is required and that is consistent with an anabolic reaction.
4. Would an increase in the concentration of glucose-6-PO 4 favor all the forward reactions where this molecule is a substrate? It might. But one must be mindful that glucose-6-PO 4 is also a regulator of enzyme activity and an increase in G6P could result in the shut down of enzymes more forward in the pathways. We’ll see allosteric effects later.
