Question

How does the hydrolysis of fructose- \(1,6-\) biphosphate bring about the reversal of one of the physiologically irreversible steps of glycolysis?

Short answer

Hydrolysis of fructose-1,6-biphosphate by fructose-1,6-bisphosphatase reverses one of the irreversible steps of glycolysis in gluconeogenesis.

Step-by-step solution

- Understanding Glycolysis

Glycolysis is a metabolic pathway that converts glucose into pyruvate, generating energy in the process. Some steps in glycolysis are physiologically irreversible due to their large negative \(\triangle G\) values.

- The Role of Fructose-1,6-biphosphate

Fructose-1,6-biphosphate is an intermediate in glycolysis created by the enzyme phosphofructokinase-1 (PFK-1). The conversion of fructose-6-phosphate to fructose-1,6-biphosphate is one of these physiologically irreversible steps.

- The Concept of Hydrolysis

Hydrolysis is a chemical process where a bond is broken by adding water. In this context, the hydrolysis of fructose-1,6-biphosphate involves breaking its phosphate bond to form simpler molecules with the aid of water.

- Reverse of Irreversible Step in Gluconeogenesis

During gluconeogenesis, the reverse process of glycolysis, the enzyme fructose-1,6-bisphosphatase catalyzes the hydrolysis of fructose-1,6-biphosphate back to fructose-6-phosphate and inorganic phosphate. This step reverses one of the irreversible steps in glycolysis, bypassing the need for PFK-1.

- Net Effect

The hydrolysis reaction does not directly produce ATP but allows the pathway to be reversed under different regulatory mechanisms, effectively bypassing the physiological irreversibility imposed by the large \(\triangle G\) of the PFK-1 catalyzed step.

Key concepts

Fructose-1,6-bisphosphate

Fructose-1,6-bisphosphate is a key intermediate within the glycolytic pathway. It is formed from fructose-6-phosphate via the enzyme phosphofructokinase-1 (PFK-1). This conversion is significant because it represents one of the 'commitment' steps in glycolysis, irreversible under normal physiological conditions due to a large negative \(\triangle G\). The molecule itself is composed of a fructose backbone with phosphate groups attached at the first and sixth carbon positions. This configuration makes it highly reactive and crucial for subsequent steps in the pathway.

Hydrolysis

Hydrolysis is a fundamental chemical reaction where a molecule is split into two parts through the addition of water. In the context of glycolysis and gluconeogenesis, the hydrolysis of fructose-1,6-bisphosphate means breaking one of its phosphate bonds to get simpler molecules. The enzyme fructose-1,6-bisphosphatase catalyzes this reaction, producing fructose-6-phosphate and inorganic phosphate. This reaction is vital in gluconeogenesis, as it reverses an otherwise irreversible step in glycolysis, thus facilitating the formation of glucose from non-carbohydrate precursors.

Gluconeogenesis

Gluconeogenesis is a metabolic pathway that produces glucose from non-carbohydrate substrates like lactate, glycerol, and certain amino acids. It primarily occurs in the liver and to a lesser extent in the kidneys. One of the interesting aspects of gluconeogenesis is that it 'reverses' certain steps of glycolysis, which is otherwise a catabolic process. Crucially, the hydrolysis of fructose-1,6-bisphosphate by the enzyme fructose-1,6-bisphosphatase bypasses the irreversible step catalyzed by phosphofructokinase-1 in glycolysis. This allows the cell to effectively 'undo' the glycolytic step and proceed with glucose synthesis.

Phosphofructokinase-1 (PFK-1)

Phosphofructokinase-1 (PFK-1) is an important regulatory enzyme in the glycolytic pathway. It catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate using ATP. This step is a significant control point in glycolysis and is heavily regulated by various factors including ATP, AMP, and citrate. Due to its high control and irreversible nature within physiological contexts, PFK-1 is one of the most studied enzymes in metabolism. Its action ensures that the glycolytic pathway commits to the breakdown of glucose for energy production. However, in gluconeogenesis, this step is bypassed by the action of fructose-1,6-bisphosphatase, allowing glucose synthesis to occur.