Question

High levels of glucose- 6 -phosphate inhibit glycolysis. If the concentration of glucose- 6 -phosphate decreases, activity is restored. Why?

Short answer

High levels of glucose-6-phosphate inhibit glycolysis by inhibiting hexokinase. Decreased glucose-6-phosphate removes this inhibition, restoring glycolysis.

Step-by-step solution

- Understand Glycolysis Regulation

Glycolysis is regulated by feedback inhibition. When there is an abundance of a downstream product like glucose-6-phosphate, certain enzymes involved in glycolysis are inhibited to prevent an overproduction of intermediates.

- Inhibition by Glucose-6-Phosphate

Specifically, glucose-6-phosphate inhibits hexokinase, the enzyme that catalyzes the first step of glycolysis, by binding to it and reducing its activity.

- Effects of Decreased Glucose-6-Phosphate

When the concentration of glucose-6-phosphate decreases, the inhibitory effect on hexokinase is reduced or removed. This allows the enzyme to become active again and resume the normal glycolysis process.

- Glycolysis Restoration

With hexokinase no longer inhibited, glycolysis continues, leading to the restoration of normal activity in the metabolic pathway.

Key concepts

Feedback Inhibition

Feedback inhibition is a fundamental mechanism in regulating metabolic pathways. It ensures that the cell does not waste resources by producing more end products than needed. In glycolysis, this regulation plays a crucial role.
When certain products accumulate in high amounts, they inhibit enzymes earlier in the pathway. This way, the production process slows down or stops. The most common example in glycolysis is the inhibition of the enzyme hexokinase.
This enzyme catalyzes the first step in glycolysis: the conversion of glucose to glucose-6-phosphate. When there's already a lot of glucose-6-phosphate, it binds to hexokinase and inhibits its activity. This prevents the unnecessary accumulation of intermediates and conserves energy and resources. It's like a stop signal telling the pathway to pause until the levels are back to normal.

Glucose-6-Phosphate

Glucose-6-phosphate is a key molecule in the regulation of glycolysis. It’s a product of the first step of glycolysis. This molecule has important roles not only in glycolysis but also in other metabolic processes.
When its levels are high, it acts as an inhibitor to the enzyme hexokinase. This feedback action is crucial. High levels signal that the cell does not need to break down more glucose into intermediates. Thus, the cell avoids wasting energy.
Once glucose-6-phosphate levels drop, it lifts the inhibition on hexokinase. This decrease is a signal that the cell can again efficiently convert glucose into glucose-6-phosphate and continue through the glycolytic pathway.
Therefore, the concentration of glucose-6-phosphate acts as a regulator, helping maintain balance in metabolic activities.

Hexokinase

Hexokinase is an essential enzyme in the glycolysis pathway. Its primary function is to catalyze the first step, converting glucose to glucose-6-phosphate.
This step is crucial since it allows the cell to trap glucose and prepare it for further breakdown to extract energy. Without hexokinase, the glycolysis pathway cannot proceed.
Hexokinase activity is regulated through feedback inhibition. When there’s too much glucose-6-phosphate, the excess binds to hexokinase, reducing its enzymatic activity. This stops further glucose from being phosphorylated.
When glucose-6-phosphate levels decrease, hexokinase is no longer inhibited and becomes active again. This reactivation allows glycolysis to resume, producing energy and metabolic intermediates needed by the cell.
By finely tuning hexokinase activity through this feedback mechanism, the cell efficiently manages its energy resources and metabolic balance.