Glycogenesis

What is glycogenesis?

It is making new glycogen

What are the four enzymes involved in glycogen synthesis? Which one is the regulatory enzyme?

1. UDP-glucose pyrophosphorylase

2. Glycogen synthase (regulatory)

3. Glycogenin

4. Branching enzyme

What does UDP-glucose pyrophosphorylase do?

It catalyzes the conversion of glucose-1-phosphate with UTP to form UDP-glucose and pyrophosphate (trying to transform glucose to UDP-glucose to activate it)

What is UDP-glucose?

It is the substrate for glycogen synthesis

What are the two reactions that can be coupled? What is the full reaction that UDP-glucose pyrophosphorylase catalyzes?

Glu-1-P + UTP (reversible arrow) UDP-glucose + PP_i

PP_i + H₂O —> 2 P_i (hydrolysis of PP_i releases energy and drives reaction forward)

Coupled: Glu-1-P + UTP —> UDP-glu + 2P_i

What does glycogen synthase do?

It elongates the alpha-1,4 linear chain by adding UDP-glucose to the non-reducing end

What is the drawback of glycogen synthase?

It cannot initiate glycogen synthesis as it requires an oligosaccharide of glucose residues as a primer. It can only add to a chain containing more than four residues.

What does glycogenin do?

It adds UDP-glucose to its tyrosine side chain through self-glucosylation until there are four or more residues so glycogen synthase can start working.

What does the branching enzyme do?

It takes a linear portion of UDP-glucose and makes a alpha-1,6 branch with it

What does branching do?

It increases the solubility of the glycogen and increases the rate of glycogen synthesis and degradation

Where do the branch points occur in glycogen synthesis?

They occur at about every 12 glucose residues.

Where does the glu-1-phosphate come from that is used to make UDP-glucose?

Glucose is converted into glucose-6-phosphate by hexokinase which uses up 1 ATP. Then glue-6-P is converted into glu-1-P through PGM (phosphoglucomutase)

What activates glycogen synthase?

Insulin, glucose, and glu-6-phosphate

High energy signals activate it

What inhibits glycogen synthase?

Epinephrine, glucagon (low energy signals), and phosphorylation

What does phosphorylation of glycogen synthase override?

Allosteric non-covalent regulators

Describe the role of glucagon in glucose homeostasis

1. Glucagon will bind to GPCR in membrane

2. GPCR will activate adenylate cyclase

3. Production of cAMP will increase

4. This activates PKA-P

5. PKA-P will phosphorylate phosphorylase kinase to activate it

6. PKA-P and phosphorylase kinase-P will inhibit glycogen synthase-P

7. Glycogen synthase-P will inhibit glycogenesis

8. Phosphorylase kinase P will phosphorylate glycogen phosphorylase

9. Glycogen phosphorylase-P will activate glycogenolysis

Describe the role of insulin in glucose homeostasis

1. Insulin will bind to insulin receptor

2. Through a series of steps phosphoprotein phosphatase I will be activated

3. Phosphoprotein phosphatase will dephosphorylate phosphorylase kinase

4. Phosphoprotein phosphatase I will dephosphorylate glycogen synthase

5. Glycogen synthase will then begin glycogenesis

6. Phosphorylase kinase will inhibit phosphorylase glycogen

7. Phosphorylase glycogen will inhibit glycogenolysis