Glycogen Degradation Flashcards
Occurs when?
Where?
What happens?
FASTED state
Liver
Break down stored glycogen
Catabolic hormones (2)
Glucagon and epinephrine
Focus in fasted state is how body maintains :
- Glucose homeostasis
2. Energy homeostasis
Ways to maintain glucose homeostasis
- Glycogen degradation
2. Gluconeogenesis
During fasted state, what happens to glucose ?
All glucose is preserved for uses by brain and RBC
Ways to maintain energy homeostasis
- Fatty acid oxidation
2. Ketogenesis
Importance of fatty acids in fasted state
FATTY ACIDS are ALTERNATIVE FUEL source in FASTED STATE
After about _____ hours after eating, glucose oxidation drops.
What do you do?
4 hours
- Begin to breakdown stored glycogen
Glycogen degradation peaks at about ____ hours without food
12
Glycogen does not last much beyond _____ hours
24
What happens along with glycogen degradation?
Gluconeogenesis
After about ___ days of fasting, gluconeogenesis declines.
Why / significance?
3 days
Fatty acids are so high in blood —> liver takes them up and oxidizes into ketone bodies which can be used as alternative energy source for glucose
Also, skeletal muscle (protein breakdown) is spared
Ketone bodies
Function?
- Glucose and protein sparing
Used as an alternative energy source for glucose when fasting.
- Oxidized in mitochondria
Ketone bodies can be used by ?
Cannot be used by?
Can be used by all tissues (even brain)
Cannot be used by RBC b/c no mitochondria to oxidize them
Conditions for degrading glycogen in muscle (3)
- During exercise
- Stress
- Elevated epinephrine
Receptors on muscle cells
NO glucagon receptors
Epinephrine receptors ONLY
Conditions that trigger glycogen degradation in liver
- Overnight fast (low I/G)
2. To some extent, epinephrine
Liver receptors
Glucagon AND epinephrine
Major enzyme in glycogen degradation
Glycogen phosphorylase
Glycogen phosphorylase attacks _____________
Alpha-1,4-glycosidic bonds
Glucose cleavage occurs at?
Non-reducing ends with a free -OH at C4
How is glucose rapidly released?
Multiple molecules of glucose can be released at once because multiple molecules of glycogen phosphorylase can be working away on same glycogen molecule starting at different branches
Type of reaction
Phosphorolysis
Glucose is released as _________
Advantage:
Glucose-1-phosphate
Advantage = do not need to use ATP
How to get glucose from the product of glycogen degradation?
G-1-P isomerizes to G-6-P —> cleave off phosphate
Phosphate donor
Phosphoric acid (HPO4 2-)
- Intracellular buffer so readily available
- Phosphate ion acts as nucleophile to split alpha-1,4-glycosidic bonds
Process of glycogen degradation
(4) enzymes
- Glycogen phosphorylase cleaves alpha-1,4-glycosidic bonds by adding a phosphate to yield G-1-P
- Transferase moves 4 residues closest to branch point to end of another branch because glycogen phosphorylase is sterically hindered
- Alpha-1,6-glucosidase cleaves branch point
- Phosphoglucomutase catalyzes isomerization of G-1-P —> G-6-P
Chemistry of phosphoglucomutase reaction
Enzyme has active site serine with phosphate on it —> Enzyme transfer its phosphate onto C-6 —> form glucose-1,6-bisphosphate —> enzyme removes phosphate from C-1 and puts it back on serine —> form glucose-6-phosphate
Fate of glucose-6-phosphate in liver
Glucose-6-phosphatase removes P to yield glucose (so transporter recognizes it)
Glucose goes into blood to maintain blood glucose homeostasis
Fate of glucose-6-phosphate in muscle
Stays in muscle
Enters glycolysis to provide ATP
Muscle cannot be used to maintain blood glucose homeostasis because (2)
- No glucagon receptors
2. Lacks glucose-6-phosphatase
Major regulated enzyme in glycogen degradation
Glycogen phosphorylase
___________ and ___________ are reversely regulated
Glycogen synthase and glycogen phosphorylase
In fasted state, glycogen synthase is __________ and ____________ by
Phosphorylated and inactivated
By glycogen synthase kinase
In fasted state, glycogen phosphorylase is ________ and _______ by
Phosphorylated and ACTIVE
Glucagon (or epi) activate PKA through cAMP which phosphorylates phosphorylase kinase which phosphorylates glycogen phosphorylase making it active
Liver condition of interest =
Fasted state
Muscle condition of interest =
Endurance exercise or stress
Increase glycogen degradation IN LIVER in response to:
Low I/G
Or epinephrine
Increase glycogen degradation IN MUSCLE in response to:
Epinephrine
Glycogen phosphorylase has ?
2 interconvertible forms: Phosphorylase a and Phosphorylase b
*each form can in the T state or R state
Phosphorylase b vs. Phosphorylase a
Phosphorylase a : always phosphorylated, more active form
Phosphorylase b : dephosphorylated, inactive form
What does phosphorylase a do?
Where?
In BOTH liver and muscle, phosphorylase a degrades glycogen.
In response to hormonal signaling in fasted state…
Phosphorylase kinase uses ATP as substrate to add phosphate group onto phosphorylase b to convert it to phosphorylase a form —>
Phosphorylase a degrades glycogen.
Predominant form in muscle
Phosphorylase b in T state
In muscle ________ is only converted to _______ with ___________.
Phosphorylase b is only converted to phosphorylase a with epinephrine signaling.
When muscle begins contraction —>
ATP levels drop —> energy charge is low so have high AMP —> AMP binds allosterically to T state of phosphorylase b —> converts it to R state
Phosphorylase b in R state
More active but NOT phosphorylated
Muscle:
Binding _____ to phosphorylase ___ in the ___ state converts it to the _______ ____ state.
Binding AMP to phosphorylase b in the T state converts it to the active R state.
Significance of AMP allosteric regulation in muscle
Allows glycogen degradation to begin before hormonal control (epi) can activate phosphorylase b to phosphorylase a
Allows contraction to continue without being starved for glucose
What connects glycolysis and glycogen degradation in muscle?
AMP
Muscle is contracting so energy charge is low.
Glucose from glycogen degradation _______________
Stays in muscle and goes through glycolysis to produce ATP
Result of AMP function in muscle
- AMP activates muscle phosphorylase b to begin degrading glycogen before it is actually phosphorylated
- AMP simultaneously stimulates glycolysis so as soon as glucose is released by glycogen degradation, it is immediately put in glycolysis pathway to alter energy change and make ATP
Predominant form in liver
Phosphorylase a in R state
In fed state, insulin signaling activates ___________ to ____________
PP1 to remove phosphate from phosphorylase a converting it to phosphorylase b, inactivating it.
As soon as blood glucose levels rise —> ______ state is converted to _____ state
R state is converted to T state
T state of phosphorylase a in liver
Less active but still phosphorylated
Significance of blood glucose control in liver
Converting phosphorylase R state to T state slows down breakdown of glycogen when the liver cells sense an increase in glucose concentration before insulin cascade can take effect
