Does substrate level phosphorylation occur during gluconeogenesis? If so, name the enzymes involved and state where substrate level phosphorylation occurs in this pathway.
The correct answer and explanation is:
No, substrate-level phosphorylation does not occur during gluconeogenesis in the direction that produces glucose. Gluconeogenesis is primarily an anabolic pathway that requires energy input, rather than producing it via substrate-level phosphorylation.
Explanation:
Substrate-level phosphorylation (SLP) is a metabolic process that generates ATP (or GTP) by the direct transfer of a high-energy phosphate group from a phosphorylated substrate to ADP (or GDP). Classic examples occur in glycolysis, where the enzymes Phosphoglycerate Kinase and Pyruvate Kinase catalyze SLP reactions, producing ATP.
Gluconeogenesis, on the other hand, is the pathway for synthesizing glucose from non-carbohydrate precursors. It is energetically expensive, requiring the hydrolysis of six high-energy phosphate bonds (4 ATP and 2 GTP) per molecule of glucose produced.
While some enzymes are shared between glycolysis and gluconeogenesis, the gluconeogenic pathway bypasses the irreversible, ATP-producing steps of glycolysis. Specifically:
- The Pyruvate Kinase step of glycolysis, which catalyzes an SLP reaction (PEP + ADP -> Pyruvate + ATP), is bypassed in gluconeogenesis by the action of Pyruvate Carboxylase (consuming ATP) and PEP Carboxykinase (consuming GTP). Neither of these bypass reactions involves substrate-level phosphorylation.
- The Phosphoglycerate Kinase step is reversible and shared. In glycolysis, it performs SLP (1,3-Bisphosphoglycerate + ADP -> 3-Phosphoglycerate + ATP). However, in gluconeogenesis, this enzyme catalyzes the reverse reaction (3-Phosphoglycerate + ATP -> 1,3-Bisphosphoglycerate + ADP), consuming ATP rather than producing it via SLP.
Therefore, the overall flux through the gluconeogenic pathway requires energy input (ATP and GTP hydrolysis) and does not include steps that result in the net production of ATP or GTP via substrate-level phosphorylation.