Question

The functioning of a particular pathway often depends not only on control enzymes in that pathway but also on control enzymes of other pathways. What happens in the following pathways under the indicated conditions? Suggest what other pathway or pathways might be influenced. (a) High ATP or NADH concentration and the citric acid cycle. (b) High ATP concentration and glycolysis. (c) High NADPH concentration and the pentose phosphate pathway. (d) High fructose- 2,6 -bisphosphate concentration and gluconeogenesis.

Short answer

High ATP/NADH inhibits the citric acid cycle. High ATP inhibits glycolysis. High NADPH downregulates the pentose phosphate pathway. High fructose-2,6-bisphosphate inhibits gluconeogenesis.

Step-by-step solution

Title - Analyze high ATP or NADH concentration's effect on the citric acid cycle

High ATP or NADH concentration signals that the cell has sufficient energy. This leads to the inhibition of certain enzymes in the citric acid cycle, specifically isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, slowing down the cycle. As a result, other pathways such as glycolysis and oxidative phosphorylation are also affected due to decreased demand for NADH and ATP production.

Title - Investigate the impact of high ATP concentration on glycolysis

High ATP concentration indicates high energy levels within the cell. This results in the inhibition of phosphofructokinase-1 (PFK-1), a key regulatory enzyme in glycolysis. When PFK-1 is inhibited, glycolysis slows down. Consequently, the pentose phosphate pathway and glycogen synthesis might also be influenced due to the shift in glucose utilization.

Title - Determine the effects of high NADPH concentration on the pentose phosphate pathway

High NADPH levels suggest that the cell’s reductive biosynthesis needs, such as fatty acid and nucleotide synthesis, are met. As a result, the pentose phosphate pathway is downregulated to avoid excess NADPH production. This may influence glycolysis and fatty acid synthesis pathways since intermediates may be redirected.

Title - Examine the influence of high fructose-2,6-bisphosphate concentration on gluconeogenesis

High levels of fructose-2,6-bisphosphate activate phosphofructokinase-1 (PFK-1) and inhibit fructose-1,6-bisphosphatase, favoring glycolysis and thus, inhibiting gluconeogenesis. This creates a shift towards glucose breakdown rather than glucose synthesis, potentially impacting glycogen synthesis and overall energy balance in the cell.

Key concepts

citric acid cycle regulation

High levels of ATP or NADH signal that the cell has enough energy reserves. In response to these high levels, the citric acid cycle slows down.
This happens because two key enzymes, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, are inhibited.
When these enzymes are less active, the whole cycle retards, which in turn affects other cellular processes.
For example, glycolysis and oxidative phosphorylation will slow down too. This is due to the reduced demand for more ATP and NADH.
In summary, when energy is plentiful, the citric acid cycle slows down to prevent energy wastage.

glycolysis regulation

When ATP levels are high, it means the cell does not need more immediate energy.
This leads to the inhibition of phosphofructokinase-1 (PFK-1), a crucial enzyme in the glycolysis pathway.
With less PFK-1 activity, glycolysis slows down. This ensures the cell does not produce excess ATP.
Besides slowing down glycolysis, other pathways are also influenced.
For instance, the pentose phosphate pathway and glycogen synthesis may change their activities due to the shifting needs.
By regulating PFK-1, the cell effectively manages its energy production and storage processes.

pentose phosphate pathway regulation

High concentrations of NADPH indicate that the cell has met its needs for reductive biosynthesis, such as fatty acid and nucleotide synthesis.
When NADPH levels are high, the pentose phosphate pathway is downregulated to avoid the excess production of NADPH.
This regulation affects other metabolic processes.
For example, intermediates that would go into the pentose phosphate pathway may now be redirected to glycolysis or fatty acid synthesis.
Overall, high NADPH levels signal the cell to balance its metabolic pathways efficiently.

gluconeogenesis regulation

Fructose-2,6-bisphosphate plays a critical role in balancing gluconeogenesis and glycolysis.
High levels of fructose-2,6-bisphosphate activate phosphofructokinase-1 (PFK-1) and inhibit fructose-1,6-bisphosphatase.
This shift causes the cell to favor glycolysis over gluconeogenesis.
As a result, more glucose is broken down rather than being synthesized.
Other pathways, such as glycogen synthesis, are also influenced because the cellular energy status changes.
The regulation of fructose-2,6-bisphosphate ensures that the cell adapts its glucose metabolism efficiently.