3 - Glycogenolysis

Under what metabolic conditions does the organism perform glycogenolysis?

The metabolic release of glucose-6-phosphate and glucose from glycogen by the action of three enzymes.

What tissues / organs are capable of performing glycogenolysis?

Tissues: All tissues are able to store glycogen to a greater or lesser extent

Organs: Liver and skeletal muscle are the major sites of glycogen storage. The kidney ranks third. Heart muscle, platelets, and adipose tissue store a small but measurable amount.

Which organ(s) perform glycogenolysis to maintain blood glucose levels?

In the liver and kidney, the stored glycogen is used to maintain blood glucose levels.

Which organ(s) perform glycogenolysis to satisfy their own metabolic needs?

Skeletal muscle – the glucose-6-phosphate enters glycolysis for energy generation

1 - What is the first enzyme in glycogenolysis and what does it do?

Glycogen phosphorylase cleaves α(1→4) glycosidic bonds at the non-reducing ends, releasing glucose-1-phosphate.

2 - What coenzyme does glycogen phosphorylase require?

Pyridoxal phosphate (PLP), a derivative of vitamin B6.

3 - What happens when glycogen phosphorylase nears a branch point?

It stops about four glucose residues before the branch due to steric hindrance.

4 - What enzyme removes branches in glycogen?

The debranching enzyme, which has two activities:

1. Transferase activity moves a trisaccharide to another branch.

2. Glucosidase activity hydrolyzes the α(1→6) bond to release free glucose.

5 - What is the fate of glucose-1-phosphate produced during glycogenolysis?

It is converted to glucose-6-phosphate by phosphoglucomutase.

What happens to glucose-6-phosphate in the liver and kidney?

It is converted to free glucose by glucose-6-phosphatase and released into the bloodstream.

What happens to glucose-6-phosphate in muscle cells?

It enters glycolysis to produce ATP; muscle cells lack glucose-6-phosphatase.

What is the net ATP yield from one glucose-1-phosphate molecule derived from glycogen (in muscle)?

3 ATP per glucose molecule, because the first ATP-consuming step of glycolysis (hexokinase) is bypassed.

Why does glycogenolysis produce more net ATP than glycolysis starting from free glucose?

Because glucose-1-phosphate from glycogen enters glycolysis as glucose-6-phosphate, avoiding the need for ATP in the phosphorylation step.

What happens to the free glucose released from α(1→6) branches during glycogenolysis?

It must be phosphorylated by hexokinase, consuming 1 ATP, yielding 2 net ATP via glycolysis.

In anaerobic glycolysis (from glycogen), what is the net ATP yield per glucose unit?

• From glucose-1-phosphate: 3 ATP

• From free glucose (from branch): 2 ATP

Name the enzyme(s) that catalyzes glycogenolysis (the release of glucose-1-phosphate and glucose of glycogen)

Glycogen phosphorylase – Cleaves α-1,4 glycosidic bonds at the non-reducing ends of glycogen to release glucose-1-phosphate (G1P)

Debranching enzyme – Hydrolyzes the remaining single glucose residue at the branch point (α-1,6 bond), releasing free glucose (not glucose-1-phosphate).

Which enzyme(s) are common to Glycogenesis and Glycogenolysis?

None! Because separate enzymes allow cells to independently regulate.

Which of the enzymes are allosteric enzymes?

Glycogen Phosphorylase A – which is controlled by reversible covalent modification.

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

In Liver – glucose inhibits Glycogen Phosphorylase A

In Skeletal Muscle – Glycogen Phosphorylase A is activated by Ca 2+ and AMP and allosterically inhibited by ATP.

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– 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.