Lecture 22, Glyc Metabolism (Zaidi) Flashcards
Describe the structure of glycogen.
Long chain homopolymer of glucose molecules with branches
What are the glucose molecules within a chain of glycogen linked together by?
alpha-1,4-glycosidic bonds
What kind of bonds are the branch points of glycogen formed by?
alpha-1,6-glycosidic
What are the 2 kinds of ends of a glycogen molecule?
Non-reducing and reducing
Describe the non-reducing end of a molecule of glycogen.
Contain a terminal glucose with a free hydroxyl group at C4
Describe the reducing end of a molecule of glycogen.
Consists of a glucose monomer connected to glycogenin
Why is glycogenin important?
Creates a short glycogen polymer on itself and serves as a primer for glycogen synthesis
From which end is glycogen degraded and extended?
Non-reducing end
Where is glycogen stored?
Liver, muscle, and other tissues
How is glycogen stored?
As granules, but the granules also contain enzymes needed for glycogen metabolism
T or F: Defects in the enzymes contained in the glycogen granules can lead to disorders.
True.
What is the function of liver glycogen?
Regulates blood glucose levels
What is the function of muscle glycogen?
Provides reservoir of fuel (glucose) for physical activity
What is an overview of glycogen metabolism?
Regulated storage and release of glucose
T or F: The synthesis and degradation of glycogen involve different pathways, but are regulated by the same mechanism.
False. The synthesis and degradation of glycogen involve different pathways and are regulated independently.
How is glycogen metabolism regulated?
Allosteric control, covalent modification through reversible phosphorylation of key enzymes, hormonal control
There are 3 key steps in glycogenesis. What is the purpose of the first step?
Trapping and activation of glucose
In glycogenesis, what traps glucose in the hepatocytes and muscle cells?
Glucokinase/hexokinase catalyze phosphorylation of glucose to glucose 6-phosphate
What enzyme reversibly isomerizes glucose 6-phosphate to glucose 1-phosphate?
Phosphoglucomutase
What is the role of uridine diphosphate (UDP) glucose pyrophosphorylase? What is generated?
Transfers the glucose 1-phosphate to UTP; UDP-glucose is generated
How does UDP glucose pyrophosphorylase generate energy?
Breakdown of pyrophosphate to Pi generates energy
What is the formation of UDP glucose catalyzed by?
UDP-glucose pyrophosphorylase
There are 3 key steps in glycogenesis. What is the purpose of the second step?
Elongation of a glycogen primer
What is the rate-limiting enzyme of glycogenesis?
Glycogen synthase
What is the enzyme that adds glucose to the preexisting glycogen polymer?
Glycogen synthase
The peexisting glycogen polymer serves as a ___ to which glucose units are added in the elongation of glycogen.
Primer
What is the mechanism of glycogen synthase? What kind of bond is formed?
Catalyzes transfer of glucose from UDP-glucose to non-reducing end of glycogen chain; Forms alpha-1,4-glycosidic bond between glucose molecules
There are 3 key steps in glycogenesis. What is the purpose of the third step?
Branching of glycogen chains
When a glycogen chain reaches about 11 residues long, what happens?
A fragment of the chain (about 7 residues) is broken off at an alpha-1,4-link and reattached elsewhere through an alpha-1,6- link
What is the enzyme that allows the branching of glycogen?
Glucosyl (4:6) transferase
How far away must a new branch point be from a preexisting branch point?
At least 4 residues away
Why is the branching of glycogen molecules important?
Branching increases solubility of glycogen and increases number of terminal non-reducing ends; Increases rate at which glycogen can be synthesized and degraded
What does the breakdown of glycogen release?
Glucose 1-phosphate
What is broken down glycogen (glucose 1-phosphate) called?
Glycogen remnant (n-1)
After glycogen breakdown, what is remodeled to permit further degradation?
Glycogen remnant
What is glucose 1-phosphate converted to? Where can this be used?
Glucose 6-phosphate; Glycolysis, free glucose for release into blood stream, PPP (NADPH and ribose derivative)
In glycogenolysis, what are the roles of the 4 key enzymes?
- Degrade glycogen (chain shortening)
2 and 3. Remodel glycogen remnants - Convert glycogen breakdown product suitable for further metabolism
What catalyzes the cleavage of glycogen?
Glycogen phosphorylase (GP)
What is the rate-limiting enzyme of glycogenolysis?
Glycogen phosphorylase (GP)
Where does chain shortening occur in glycogenolysis?
Non-reducing end of polymer
What is the mechanism of GP?
Adds orthophosphate and releases glucose residue as G1P; Uses pyridoxal phosphate (vitamin B6) as a cofactor
How long does the phosphorolysis of glucose residues continue?
Until the GP gets within 4 residues of the alpha-1,6-linkage of a branch point
What is the role of phosphoglucomutase?
Converts G1P to G6P
What is the mechanism of phosphoglucomutase?
Phosphoryl group is transferred form enzyme to the substrate, and a different phosphoryl group is transferred back to restore the enzyme to its initial state
What is the role of transferase in glycogenolysis?
Transfers a block of 3 of the remaining 4 glucose to the non-reducing end of the main chain forming an alpha-1,4 bond
What is the role of the debranching enzyme (alpha 1,6 glucosidase)?
Cleaves alpha-1,6 bond of single remaining glucose residue to release the free glucose
In glycogenolysis, what is glucose phosphorylated by?
Hexokinase
What enzymes convert branched glycogen into a linear structure for further action by GP?
alpha-1,6-glucosidase and transferase
T or F: G6P cannot get out of the cell.
True.
Which is the only organ that has glucose 6 phosphatase?
Liver
What does the liver do with glucose 6 phosphatase?
Converts G6P to glucose, which can be released in the bloodstream
