In an erythrocyte undergoing glycolysis, what would be the effect of a sudden increase in the concentration of a. ATP? b. AMP? c. fructose- 1,6 -bisphosphate? d. fructose- 2,6 -bisphosphate? e. citrate? f. glucose- 6 -phosphate?

When it comes to the regulation of glycolysis, ATP plays a pivotal role. Glycolysis is the metabolic pathway that converts glucose into pyruvate, generating a small amount of ATP in the process. But when the cell already has high levels of ATP, the cell aims to prevent an excessive accumulation of this energy currency.

High levels of ATP inhibit a key enzyme in glycolysis called Phosphofructokinase-1 (PFK-1). ATP binds to a specific regulatory site on the enzyme, distinct from the active site, and reduces its activity. This is an example of feedback inhibition — the end product of a pathway (ATP) inhibits an early step (PFK-1 activity) to prevent the production of more end product.

This inhibition is vital for energy conservation within the cell, ensuring that glucose isn't broken down unnecessarily when there's already sufficient energy available. But if the need for energy increases, such as during muscle exertion, ATP levels would fall, alleviating the inhibition on PFK-1, and glycolysis would resume to meet the demand for more ATP.

In contrast to ATP, AMP signals a low energy state within the cell and thereby stimulates glycolysis to replenish ATP levels. AMP, which arises from ATP depletion, binds to PFK-1 and enhances its activity. This activation of PFK-1 is another form of allosteric regulation, where the binding of an effector molecule (AMP) at one site on an enzyme affects the activity at a different site.

This effect of AMP ensures that when the cell's energy supply runs low, the glycolytic pathway ramps up to speed up the production of ATP. Phosphofructokinase-1, being one of the key regulatory points of the glycolytic pathway, is the main control point where AMP exerts its stimulating effect. By influencing PFK-1, AMP increases the metabolic flow through the glycolytic pipeline, leading to increased generation of ATP and, thus, rebalancing the cellular energy state.

Fructose-2,6-bisphosphate is another powerful regulator of glycolysis, but its role is distinct and more nuanced than that of ATP or AMP. This molecule acts as a highly potent allosteric activator of Phosphofructokinase-1 (PFK-1), overriding even the inhibitory effects of ATP on this enzyme.

The synthesis of fructose-2,6-bisphosphate is regulated by a separate enzyme called Phosphofructokinase-2 (PFK-2), which is responsive to hormonal signals, particularly insulin. When insulin levels are high, such as after consuming a carbohydrate-rich meal, PFK-2 is activated and produces more fructose-2,6-bisphosphate, signaling that excess glucose should be utilized for energy and storage pathways.

The elevation in fructose-2,6-bisphosphate levels leads to a stimulation of glycolysis and a reduction of gluconeogenesis— the process of generating glucose from non-carbohydrate sources. This regulation ensures that when glucose is abundant, it is efficiently converted to energy and stored, while also preventing the wasteful cycle of simultaneously making and using glucose within the cell.