2.9 Glycogen Metabolism Flashcards
Define glycogen
A soluble polymer of many glucose units
Define glycogenesis
Intracellular synthesis of glycogen from glucose
- Occurs in cytosol of liver and muscle cells
Define Glycogenolysis
Intracellular breakdown of glycogen to form glucose
- Breakdown of glycogen
Describe liver glycogen
- Short term energy
- Liver stores and releases glucose from glycogenolysis in response to low blood glucose levels
- Puts glucose back in blood when brain needs it
Describe muscle glycogen
- Main fuel substrate during high intensity exercise within muscle cells
- Depleted after prolonged exercise
Why store glucose as glycogen?
A large amount of glucose can’t be in cells b/c accumulation of charged G-6-P has strong osmotic effect (cells swell)
Is glycogen charged or uncharged?
Not charged
A non-branched structure doesn’t allow for
Rapid synthesis and breakdown
Glycogen core complexes consist of
Glycogenin protein
Glycogen synthesis involves
Elongation of linear chains and formation of branch points
Glycogen degradation involves
Sequential removal of glucose and the disassembly of branch points
What are the enzymes of glycogenesis?
Glucokinase
Phosphoglucomutase
UDPG pyrophosphorylase
Glycogen synthase
Glycogenesis is stimulated by
Insulin in the liver and muscle
Enzymes involved in glycogenolysis
Phosphorylase
Phosphoglucomatuse
Glucose-6-phosphatase
Glycogenolysis is stimulated by
Glucagon in the liver and epinephrine in muscle
Most glycogen synthesis occurs via addition of glucose residues to a
preexisting glycogen molecule
In the absence of a preexisting glycogen molecule, the protein ___ serves as a ___
glycogenin
primer
Describe phosphoglucomutase (PGM)
Catalyzes G-1-P and G-6-P
- It’s required for both synthesis and degradation of glycogen
- Moves phosphate from position 6 to 1
The first committed step in glycogen synthesis is the formation of
Uridine diphosphate (UDP) glucose
Hydrolysis of PPi (when UDP glucose is the enzyme) drives glycogen synthesis and prevents a ___
Potential futile cycle
- Not reversible
Describe glycogen synthase rxn
Glycogen chains are elongated 1 UDP-glucose unit at a time via glycogen synthase
What bond is formed between UDP-glucose and a glycogen end
alpha-1,4-glycosidic bond
What transfers 7 glucose units from the end of the chain to an internal position using a alpha-1,6-branch point?
glycogen branching enzyme (1,4-alpha-glucagon-branching enzyme)
- Does this once it reaches 11 glucose residues
What is the first step in glycogenolysis?
Glycogen phosphorylase catalyzes glycogen to glucose-1-phosphate + glycogen
Glycogen phosphorylase breaks the ___ bond, but NOT the ___
Breaks = 1,4 bond
DOESN’T break = 1,6 bond
What does glycogen transferase do?
Removes 3 glucose units by breaking a 1,4 bond on one strand and forming a new 1,4 bond on another
What enzyme breaks the 1,6 bond?
Debranching enzyme (alpha 1,6-glucosidase)
Does the debranching enzyme remove a glucose or glucose-1-phosphate unit?
Glucose
Complete degradation of glycogen releases ___% of glucose-1-phosphate and ___% glucose moleucles
90%
10%
What is the second enzyme used in glycogenolysis and what does it do?
Phosphoglucomutase
G-1-P to G-6-P
What is the third enzyme involved in glycogenolysis and what does it do?
Glucose-6-phosphatase
G-6-P to glucose
Where is glucose-6-phosphatase located and why?
Integral membrane protein of the ER because it separates reaction from glycolysis
What’s the process for dephosphorylation of G6P to glucose?
- G-6-P is transported to ER lumen by a specific transporter (T1)
- G-6-P is hydrolyzed by glucose-6-phosphatase
- Glucose is transported to cytosol via transporter T2 and out of cell via GLUT2
What activates glycogen phosphorylase in muscles?
Calcium
What happens to glycogen phosphorylase in the liver?
It’s inhibited
Glycogen synthase and glycogen phosphorylase respond in opposite ways to phosphorylation, GS is ___ and GP is ___
GS = inactivated GP = activated
Muscles don’t respond to glucagon, so what triggers the same pathway?
epinephrine
When going from G-1-P to glycogen, what enzymes are added to glycogen synthase?
Protein kinase A tries to add P from cAMP, but it negatively regulates it
SO
Protein phosphatase from insulin removes a P
When going from glycogen to G-1-P, what enzymes are involved with P?
Protein phosphatase from insulin removes P
SO
Phosphorylase kinase from glucagon in liver, and epinephrine in muscle adds a P and activates GP to breakdown glycogen
Fasting does what
Phosphorylates
Insulin ___, leading to the activation of pyruvate kinase, pyruvate dehydrogenase and glycogen synthase
Dephosphorylates
Glucagon leads to phosphorylation of what enzymes? Are they active or inactive?
Pyruvate Kinase (glycolysis) = INACTIVE Pyruvate dehydrogenase (Pyruvate to Acetyl Co-A) = INACTIVE Glycogen Synthase (glycogen synthesis) = INACTIVE Glycogen phosphorylase (glycogen breakdown) = ACTIVATION
Insulin is required for storing ___
Glucose as glycogen
Glucagon is required for releasing ___
Glucose from its stores in the liver
What is glycogen storage disease (GSD)?
Defect in any one of the several enzymes required for either glycogen synthesis or degradation
What 2 ways can GSDs be divided into?
- Hepatic involvement (hypoglycemia)
- Those with neuromuscular disease and weakness
