Glycogen Metabolism Flashcards
1
Q
3 strategies in maintenance of blood glucose
A
- diet
- glycogen
- gluconeogenesis
2
Q
Glycogen
A
- Liver glycogen is rapidly mobilised in response to falling blood glucose levels
- Muscle glycogen is degraded in exercising muscle to provide the tissue with energy
3
Q
Gluconeogenesis
A
- newly synthesised glucose from non-carbohydrate sources ensures blood glucose levels are maintained in the absence of glycogen
4
Q
Glycogen structure
A
- Polymers of α-D-glucose
- Main chains α(1-4) glycosylic bonds, branches α(1-6) linkages
- Branched occur every 8-12 residues
5
Q
First step in glycogenesis
A
- Glucose phosphorylation
- conversion of glucose to G-6-P
- catalysed by hexokinases (glucokinase among them)
6
Q
Second step in glycogenesis
A
- Glucose-1-phosphate formation
- phosphoglucomutase catalyses transfer of phosphate group from carbon 6 to carbon 1 on the glucose molecule
- G-6-P converted to glucose-l-phosphate
- Phosphoglucomutase requires Mg+ and glucose-1,6-bisphosphate as cofactors
- reaction is reversible
7
Q
Bisphosphates and diphosphates
A
- bisphosphate: 2 phosphates bound at different sites on same molecule
- diphosphate: phosphates bound together by anhydride bond i.e. ADP
8
Q
Third step in glycogenesis
A
- Glucose activation
- G-1-P reacts with high energy nucleotide uridine triphosphate (UTP) to give uridine diphosphate glucose (UDPG) and pyrophosphate (PPi)
- catalysed by uridine diphosphate-glucose pyrophosphorylase, or glucose-1-P uridyltransferase
- Inorganic pyrophosphate rapidly hydrolyzed by pyrophosphatase, this reaction virtually irreversible
9
Q
Fourth step in glycogenesis
A
- Glucose addition to the polymer backbone
- UDPG-activated glucose is transferred to pre-existing glycogen
- One glycosidic linkage to carbon 4 of a terminal glucose of a glycogen chain is formed
- catalysed by glycogen synthase, requires presence of the pre-existing glycogen polymeric structure, which keeps adding glucose molecules via α1-4 bonds
- reaction is practically irreversible
10
Q
Fifth step in glycogenesis
A
- branch formation
- when glycogen synthase has built a glycogen chain of 10 or more glucose residues, another enzyme, amylo-α(1,4)-α(1,6)-glucantransferase (or branching enzyme), cuts a terminal segment of at least 6 glucose molecules and inserts it with an α1-6 glycosidic bond on a neighboring chain
- further elongation and branching forms glycogen
11
Q
Glycogenin
A
- acts as an acceptor of the first glucose molecule prior to the glycosidic linkage with a tyrosine protein
- process is autocatalytic, using UDPG as glucose donor
- catalyses the successive addition of units to form a linear chain from six to seven glucose molecules bound by α1-4 bonds
- Each glycogen molecule is covalently linked to an initiator protein
12
Q
Step 1 in glycogenolysis (glycogen degradation)
A
- glycogen phosphorylase cleaves α-1,4-glycosidic bonds of terminal glucose residues at non-reducing end of glycogen (i.e. the end of the glycogen molecule with a free 4-OH group)
until only four glucosyl units remain on each chain before a branch point - inorganic phosphate, cleaves glycosidic bond between C1 of terminal residue and C4 of adjacent glycogen molecule via phosphorolysis to yield glucose 1-phosphate
13
Q
Step 2 of glycogenolysis (glycogen degradation)
A
- debranching enzyme (with 4:4 transferase activity) shifts a block of 3 glycosyl residues from one outer branch to non reducing end
- remaining single glucose molecule has a α-1,6-glycosidic bond joined to the glycogen molecule
14
Q
Step 3 of glycogenolysis (glycogen degradation)
A
- the same debranching enzyme (also with amylo-a(1-6)-glucosidase activity) cleaves the linkage and results in the release of a free glucose molecule
- steps 1, 2 and 3 are repeated
15
Q
End products of glycogenolysis in the liver
A
- phosphoglucomutase is used to convert glucose 1-phosphate formed in the cleavage of glycogen into glucose 6-phosphate to enter the metabolic mainstream
- glucose 6-phosphatase converts the glucose 6-phosphate into glucose by cleaving the phosphoryl group
16
Q
End products of glycogenolysis in muscle cells
A
- hexokinase or glucokinase will metabolise glucose 6-phosphate to either pyruvate (aerobic conditions) or lactate (anaerobic conditions)
17
Q
Regulation of glycogen metabolism in liver
A
- well fed state: glycogenesis increases
- fasting state: glycogenolysis increases
18
Q
Regulation of glycogen metabolism in muscle
A
- Active exercise: glycogenolysis begins
- Resting muscle: glycogenesis begins
19
Q
PKA
A
- cAMP-dependent protein kinase A
20
Q
Hormone Regulation of Glycogen Metabolism via PKA
A
- fasting state: decrease in blood glucose, decrease in release of insulin, increase in release of glucagon, increase in PKA activity
- activation of the counter-regulatory response, epinephrine release from adrenal medulla, increase in PKA activity
21
Q
Glycogen phosphorylase exist in what 2 forms?
A
- Active [phosphorylated]
- Inactive [dephosphorylated]
22
Q
Effect of active PKA on Glycogen Phosphorylase
A
- Phosphorylated states of glycogen phosphorylase kinase and glycogen phosphorylase are maintained because protein phosphatase-1 is inactivated by inhibitor proteins that are also activated in response to cAMP.
- Insulin (well-fed state) increases phosphatase activity and leads to inactivation of glycogen phosphorylase
23
Q
Glycogen synthase exists in what 2 forms?
A
- Active [dephosphorylated]
- Inactive [phosphorylated]
24
Q
Allosteric Regulation of Glucogenesis & Glycogenolysis
A
- Glycogenesis is stimulated when glucose and energy is high
- Glycogenolysis is stimulated with glucose and energy is low
- During muscle contraction, ATP is supplied be the degradation of muscle glycogen to glucose 6P, which enters glycolysis.
- Glycogen phosphorylase kinase increases active form w/o the need to be phosphorylated by PKA (↑glycogenolysis)
