Question

How does glucagon affect the following enzymes: (a) Glycogen phosphorylase (b) Glycogen synthase (c) Phosphofructokinase I

Short answer

Glucagon activates glycogen phosphorylase, inhibits glycogen synthase, and reduces phosphofructokinase I activity indirectly.

Step-by-step solution

- Understanding Glucagon

Glucagon is a hormone produced by the pancreas that raises blood glucose levels by promoting glycogen breakdown and glucose production. It acts primarily on the liver.

- Glucagon Effect on Glycogen Phosphorylase

Glucagon activates glycogen phosphorylase through a cascade that results in the phosphorylation of this enzyme. Phosphorylated glycogen phosphorylase becomes active and breaks down glycogen into glucose-1-phosphate.

- Glucagon Effect on Glycogen Synthase

Glucagon inhibits glycogen synthase by promoting its phosphorylation. Phosphorylated glycogen synthase is inactive, reducing the synthesis of glycogen from glucose.

- Glucagon Effect on Phosphofructokinase I

Glucagon inhibits phosphofructokinase I indirectly by decreasing the levels of fructose-2,6-bisphosphate, an allosteric activator of phosphofructokinase I. This reduces the rate of glycolysis.

Key concepts

Glycogen Phosphorylase Activation

Glycogen phosphorylase plays a crucial role in breaking down glycogen into glucose-1-phosphate. This breakdown is vital for maintaining blood glucose levels, especially during fasting or intense exercise.
Glucagon, a hormone released by the pancreas, acts when blood sugar levels are low. It triggers a series of events leading to the activation of glycogen phosphorylase.
The mechanism starts with glucagon binding to its receptor on liver cells. This binding activates enzymes and proteins inside the cell, including the phosphorylation of glycogen phosphorylase.

Phosphorylation is the addition of a phosphate group, which is done by an enzyme called phosphorylase kinase. Once phosphorylated, glycogen phosphorylase switches to its active form and begins breaking down glycogen.
The result is the production of glucose-1-phosphate, which can quickly turn into glucose-6-phosphate and then into free glucose.
This free glucose is released into the bloodstream to keep energy levels stable when you're in need of a quick boost.

Glycogen Synthase Inhibition

Glycogen synthase is key for the synthesis of glycogen from glucose. This process is important for storing energy for later use.
When glucagon levels rise, it signals that the body needs more glucose in the blood, rather than storing it in the liver.
To achieve this, glucagon inhibits the action of glycogen synthase.
Similar to glycogen phosphorylase, this inhibition happens through phosphorylation, but this time the phosphorylation inactivates the enzyme.
When glycogen synthase is phosphorylated, it stops converting glucose into glycogen.
This inhibition prevents the storage of glucose, ensuring that it remains available in the blood to meet the body’s immediate energy needs.
Such regulation helps balance the availability of glucose for quick energy versus its storage for future use.

Phosphofructokinase I Inhibition

Phosphofructokinase I (PFK-1) is a key enzyme in glycolysis, the process of breaking down glucose for energy.
It helps convert fructose-6-phosphate into fructose-1,6-bisphosphate, driving the process forward.
Glucagon inhibits PFK-1 indirectly by reducing the levels of fructose-2,6-bisphosphate (F-2,6-BP).
F-2,6-BP is an important molecule that normally activates PFK-1, enhancing glycolysis.
When glucagon is released, it activates an enzyme that breaks down F-2,6-BP.
Lower levels of F-2,6-BP mean that PFK-1 is less active, slowing down glycolysis.
This reduction in glycolysis is part of the body’s strategy to make more glucose available in the bloodstream, rather than being used up immediately for energy.
It ensures a steady supply of glucose for vital organs during periods of low blood sugar. This regulation helps the body adapt quickly to changes in energy demand.