Lecture 22

Question 1

State the name for a homopolymer of glucose. Describe the significance of alpha-1,4 glycosidic bonds and alpha-1,6 glycosidic bonds in the structure of this.

Answer 1

Glycogen

alpha-1,4 glycosidic bonds hold the glucose molecules together in a chain

alpha-1,6 glycosidic bonds form “branch points” between glucose monomers of separate chains

Question 2

Glycogen is degraded and extended from it’s __-____end. Compare each end of a glycogen molecule

Answer 2

non-reducing end

Non-reducing end contains a terminal glucose with a free hydroxyl group at C4

The reducing end consists of a glucose monomer connected by “glycogenin” (a protein that serves as a primer for glycogen synthesis)

Question 3

Describe how glycogen in stored and how a defect in this method can lead to disorders.

Answer 3

glycogen is stored in granules which contain glycogen and the enzymes needed to conduct glycogen metabolism

defects in these enzymes can cause problems (disorder)

Question 4

Compare the functions of glycogen in the live and in muscles

Answer 4

Liver glycogen: regulates blood glucose levels

Muscle glycogen: provides a reservoir of glucose for physical activity

Question 5

State the 3 methods by which the synthesis/degradation of glycogen are regulated.

Answer 5

1. Allosteric control (changing the conformation of the enzymes)
2. Covalent modification (reversible phosphorylation of enzymes)
3. Hormonal control (“The big daddy”)

Question 6

State the 3 “key steps” of glycogenesis

Answer 6

1. Trapping and Activation of Glucose
2. Elongation of a glycogen primer
3. Branching of glycogen chains

Question 7

The first step of Glycogenesis begins with glucose and ends with UDP-glucose. Describe it.

Answer 7

Glucose (via hexokinase and ATP consumption) becomes Glucose-6-P

Glucose-6-P (via phosphoglucomutase (PGM)) becomes Glucose-1-P

Glucose-1-P (via UDP-glucose pyrophosphate and UTP consumption) becomes UDP-Glucose

Question 8

What makes the first step of glycogenesis an “energetically favorable” reaction, despite it’s consumption of ATP and UTP?

Answer 8

When UTP is consumed, it is released as PPi

PPi can be broken down into 2 Pi molecules and this reaction generates energy

Question 9

What is the rate limiting step of glycogenesis? what does this enzyme catalyze?

Answer 9

The Glycogen synthase enzyme

It catalyzes the transfer of glucose from UDP-glucose to the non-reducing end of a glycogen chain (forms an alpha-1,4 glycosidic bond to attach it to the chain)

Question 10

Describe the enzyme that catalyzes the “branching” of glucose chains that compose a glycogen molecule, what number of linear glucose molecules does this occur at, and what type of link it uses to form a “branch”.

Answer 10

Glucosyl transferase (4:6 transferase) creates an alpha-1,6 glycosidic bond to form branched glucose chains in a glycogen molecule

“branching” occurs when 11 linearly bonded glucose molecules are created (11 is where the branching begins ; “too long to not be branched”)

Question 11

No matter which pathway the glycogen will be consumed by, it will reach a point during glycogenolysis where it is glucose-6-phosphate. State the final product of the following pathways that glucose-6-phosphate can follow after glycogenolysis.

Muscle/Brain:

Liver:

Pentose Phosphate pathway:

Answer 11

Muscle/Brain: it eventually becomes pyruvate (which is broken down into lactate + CO2 + H2O to produce energy)

Liver: it eventually becomes free glucose that enters the blood

Pentose Phosphate pathway: it eventually becomes Ribose + NADPH

Question 12

Describe the process of glycogenolysis (3 structures 2 enzymes)

Answer 12

Glycogen (via Glycogen phosphorylase using vitamin B6 as a cofactor) becomes Glucose-1-phosphate

Glucose-1-phosphate (via phosphoglucomutase) becomes Glucose-6-phosphate

Question 13

There are 4 key enzymes involved in glycogenolysis. Match them up with the following functions

one to degrade glycogen

two to remodel glycogen remnants

one to convert glycogen breakdown product to make it suitable for further metabolism.

Answer 13

GP (glycogen phosphorylase): degrades glycogen
Transferase: moves a block of 3 glucose to the “main branch” of glycogen (leaves 1 glucose)

Alpha-1,6-glucosidase: removes the remaining glucose from a degraded glycogen chain by cleaving the alpha-1,6 bond

Phosphoglucomutase: converts glucose-1-phosphate to glucose-6-phosphate

Question 14

What is the rate limiting enzymes for glycogenolysis? explain it’s function

Answer 14

Glycogen Phosphorylase (GP): adds an orthophosphate to the non-reducing end of glycogen, which releases a glucose-1-phosphate from the chain

Question 15

What cofactor does Glycogen phosphorylase (GP) require? how short must the glycogen chain become before GP stops removing glucose from the chain?

Answer 15

pyridoxal phosphate (Vitamin B6)

phosphorolysis of glucose continues until there are only 4 glucose residues between GP and the alpha-1,6 glycosidic bond (signals the “branch point”)

Question 16

Describe the function/mechanism of phosphoglucomutase in glycogenolysis

Answer 16

phosphoglucomutase converts glucose-1-phosphate into glucose-6-phosphate

It forms a glucose-1,6-bisphosphate intermediate while it does this bc it removes a phosphate and adds a DIFFERENT phosphate molecule
(it does NOT just move the original phosphate)

Question 17

Since,during glycogenolysis, glycogen phosphorylase (GP) stops when there are 4 glucose residues left on a glycogen branch. Explain the 2 other enzymes that act to eliminate the 4 glucose residues left on a branch.

Answer 17

Transferase: moves a block of 3 glucose residues to the non-reducing end of an adjacent “main” chain

Alpha-1,6 glucosidase: cleaves the alpha-1,6 glycosidic bond that is holding the last remaining glucose residue of the branch. (Once that glucose is freed, hexokinase phosphorylates it)

Question 18

True or False:
alpha-1,6 glucosidase and Transferase convert branched chains of glucose in a glycogen molecule into linear chains. explain.

Answer 18

True

transferase moves 3 into a linear chain

alpha-1,6 glucosidase removes the last glucose by breaking it’s alpha-1,6 bond

Question 19

What is the “yield” after debranching a single branch of a glycogen molecule?

Answer 19

a chain of 10 glucose-1-phosphate molecules and 1 molecule of free glucose

Question 20

Explain the action of glucose-6-phosphatase and why it is important for this to occur in the liver.

Answer 20

glucose-6-phosphatase removes a phosphate from glucose-6-phosphate, creating free glucose

this must occur in the liver bc glucose-6-phosphate cannot exit the cell, so free glucose must be made so that it can leave the liver via the bloodstream
(this does not occur in muscle cells bc they do not have the glucose-6-phosphatase enzyme)

Question 21

State the enzyme that allows there to be a very small amount of glycogenolysis occuring in an organelle that is not the mito.

Answer 21

lysosomal alpha-1,6 glucosidase (acid maltase)