2 - Glycogenesis

Describe the process of glycogenesis

The pathway that stores glucose as glycogen.

Under what metabolic conditions does the organism perform glycogenesis

In conditions of high blood glucose concentrations.

What tissues / organs are capable of performing glycogenesis?

Major: Liver and skeletal muscle.

Lesser: Kidney, heart, platelets, adipose tissue

What is the purpose of glycogenesis in the liver?

Store excess glucose as glycogen – will be released later when the body needs energy.

Functions:

• Regulates blood glucose levels

• Energy reserve

• Metabolic buffer

What is the purpose of glycogenesis in the other tissues?

Local use only!

Skeletal muscle – provides energy for muscle contraction during activity.

Lesser sites: local energy reserve to support its own function under specific conditions.

1 - What is the first step of glycogenesis?

Glucose is phosphorylated to glucose-6-phosphate by hexokinase (in muscle) or glucokinase (in liver).

2 - What enzyme converts glucose-6-phosphate to glucose-1-phosphate?

Phosphoglucomutase

3 - How is glucose-1-phosphate activated for glycogen synthesis?

It reacts with UTP to form UDP-glucose and pyrophosphate, catalyzed by UDP-glucose pyrophosphorylase.

4 - What is the role of UDP-glucose in glycogenesis?

It serves as the glucose donor for glycogen synthesis.

5 - What enzyme transfers glucose from UDP-glucose to a growing glycogen chain?

Glycogen synthase.

6 - Where does glycogen synthase add glucose on the glycogen molecule?

To the C-4 hydroxyl group of a glucose residue at the non-reducing end.

7 - What enzyme introduces α(1→6) branches in the glycogen molecule?

The branching enzyme (also called amylo-(1,4→1,6)-transglycosylase).

8 - How does the branching enzyme function in glycogenesis?

It removes a 6-7 glucose residue segment from the end of a chain and attaches it via an α(1→6) linkage to a more interior site.

Which enzyme phosphorylates glucose to form glucose-6-phosphate?

Hexokinase

What happens to glucose-6-phosphate in the cell?

It forms a metabolic pool from which various pathways, including glycogenesis, draw substrates.

What enzyme converts glucose-6-phosphate to glucose-1-phosphate in glycogenesis?

Phosphoglucomutase.

How is glucose-1-phosphate activated for glycogenesis?

It is coupled to UTP by UDP-glucose pyrophosphorylase, forming UDP-glucose and pyrophosphate.

Why is the formation of UDP-glucose considered energy expensive?

Because coupling glucose-1-phosphate to UTP and hydrolyzing pyrophosphate consumes a large amount of energy.

What enzyme adds glucose to a growing glycogen chain?

Glycogen synthase.

Where does glycogen synthase add glucose in the glycogen molecule?

To the C-4 hydroxyl group at the non-reducing ends of the growing glycogen chain.

Name the enzyme(s) that catalyzes the reactions glycogenesis.

1. Hexokinase

2. Phosphoglucomutase

3. UDP-glucose pyrophosphorylase

4. Glycogen synthase

Which of the enzymes are allosteric enzymes?

Glycogen synthase (main) – reversible covalent modification

Describe the allosteric effectors and how the enzyme(s) are affected.

Glucose-6-phosphate (G6P) binds to glycogen synthase allosterically. This indices a conformational change that enhances enzyme activity.

*important because this allows the body to respond quickly to changes in glucose availability without waiting for hormonal signals.

Compare / Contrast the control points in glycogenesis with the control points of glycogenolysis.

Glycogenesis– high concentration of glucose activates, low concentration of glucose inhibits

Glycogenolysis– in liver, glucose concentration. Skeletal muscle, glucose concentration and energy. AMP activates, ATP inhibits.

Compare / Contrast the allosteric effectors of glycogenesis with the allosteric effectors of glycogenolysis.

Glycogenesis– concentration of glucose

Glycogenolysis– in liver, glucose concentration. Skeletal muscle, glucose concentration and energy. AMP activates, ATP inhibits