Question

In metabolism, glucose- 6 -phosphate (G6P) can be used for glycogen synthesis or for glycolysis, among other fates. What does it cost, in terms of ATP equivalents, to store G6P as glycogen, rather than to use it for energy in glycolysis? Hint: The branched structure of glycogen leads to \(90 \%\) of glucose residues being released as glucose- 1 -phosphate and \(10 \%\) as glucose.

Short answer

Storing G6P as glycogen rather than using it in glycolysis costs 0.1 ATP per G6P molecule.

Step-by-step solution

Understand Conversion

First, glucose-6-phosphate (G6P) is converted to glucose-1-phosphate (G1P), an isomerization reaction that does not cost any ATP.

Phosphorolysis of Glycogen

For each glucose molecule stored in glycogen, about 90% are released as glucose-1-phosphate. Glucose-1-phosphate then isomerizes to glucose-6-phosphate (G6P), costing no ATP. The remaining 10% are released as free glucose, which requires phosphorylation by hexokinase to become G6P, costing 1 ATP.

Calculate the Cost for 100 Glucose Molecules

For 100 glucose molecules, 10% or 10 molecules are released as free glucose. Each of these 10 glucose molecules requires 1 ATP to be phosphorylated to G6P. Thus, the total ATP cost for 10 molecules is 10 ATP.

Total Cost in ATP Equivalents

Since 90% of G6P does not cost any ATP and 10% costs 1 ATP each, the total cost in ATP equivalents to store G6P as glycogen rather than to use it in glycolysis is 10 ATP for every 100 glucose molecules.

Key concepts

Glucose-6-Phosphate: Central Metabolite

Glucose-6-phosphate (G6P) is a crucial molecule in cellular metabolism. It serves as an intersection point for multiple metabolic pathways. G6P can be derived from glucose through the action of an enzyme called hexokinase, using ATP. It can also be formed from glycogen breakdown through phosphorolysis, which doesn't cost ATP. Its importance lies in its versatility:

• It can enter glycolysis to provide energy.
• It can contribute to the synthesis of glycogen for energy storage.
• It participates in various biosynthetic pathways, depending on cellular needs.

Glycogen Synthesis: Energy Storage

Glycogen synthesis is the process of converting glucose into glycogen for storage in the liver and muscles. It starts with G6P, which is converted to glucose-1-phosphate (G1P) through an isomerization reaction that does not require ATP.
G1P then reacts with a molecule called UTP to form UDP-glucose, which is the substrate for glycogen synthase. This enzyme adds glucose units to a growing glycogen chain. Because of the branched structure of glycogen, approximately 90% of glucose residues will eventually be released as G1P, and about 10% as free glucose.
Free glucose needs phosphorylation by hexokinase to be converted back to G6P, costing 1 ATP per free glucose molecule.

Glycolysis: Pathway for Energy Production

Glycolysis is a series of reactions that break down glucose (or G6P) to produce energy in the form of ATP. The pathway consists of ten enzyme-catalyzed steps and occurs in the cytoplasm of cells.
When G6P enters glycolysis, it eventually splits into two molecules of pyruvate, generating a net yield of 2 ATP molecules and 2 NADH per glucose molecule. Therefore, choosing to put G6P through glycolysis rather than storing it as glycogen directly produces energy, useful for immediate cellular functions.
In situations where the body needs a quick supply of energy, glycolysis is a fast and efficient pathway to follow.

Phosphorylation: The Key Reaction

Phosphorylation is the addition of a phosphate group to a molecule, often using ATP as the phosphate donor. In the context of glucose metabolism:

• Hexokinase phosphorylates free glucose to form G6P, using 1 molecule of ATP.
• Phosphorylation reactions are essential for activating molecules and driving metabolic processes.
• During glycogen breakdown, free glucose released from glycogen must be phosphorylated to re-enter pathways like glycolysis.

This reaction is crucial for maintaining the levels of G6P necessary for cellular activities, especially in muscles and the liver, where glucose has multifaceted roles.

Hexokinase: The Phosphorylation Catalyst

Hexokinase is an important enzyme that catalyzes the phosphorylation of glucose to G6P. This reaction is the first step of glycolysis but also crucial in glycogen breakdown.
Hexokinase ensures that free glucose, either from dietary intake or released from glycogen, is trapped within cells by converting it to G6P. This prevents glucose from leaving the cell and prepares it for further metabolic processes.
Despite its importance, hexokinase's activity has a cost: it uses 1 ATP per phosphorylation. This is an important point when considering the energy balance in pathways like glycogen synthesis.

• Works in the cytoplasm
• Highly specific for glucose
• Regulated by feedback inhibition