Glycogen Metabolism Flashcards
1
Q
What is glycogen
A
- storage form of glucose (polymer) that is easily mobilised
- store in the liver and muscle to maintain blood glucose and help muscle contraction
2
Q
Glycogen structure
A
- chain of glucose units linked with a1-4 and a1-6 glycosidic bonds
- branching gives many ends and increases storage potential
3
Q
Glycogen Synthesis
A
- glycosidic bond formation needs nucleotide sugar (activated form)
- UDP-glucose
- OH attacks and displaces UDP
- addition on nonreducing end (C4 hydroxyl)
4
Q
UDP Glucose
A
- nucleotide sugar donor
- glucose attached to two phosphates, a ribose sugar, and a uracil base
5
Q
Glycogen Synthase
A
- catalyses glucose transfer from UDP-glucose to hydroxyl on C4 of glucose at non reducing end
- requires preformed a1-4 linked chain (of minimum 8 residues) before it can work
- active dephosphorylated a form vs. non active phosphorylated b form
6
Q
Glycogen Branching
A
- glycogen branching enzyme (glycosyl 4-6 transferase)
- transfer of terminal 6/7 glucose residues from non-reducing end of a glycogen chain of at least 11 residues to C6-OH of a glucose at interior residues
- creates a new branch with more non reducing ends available for glycogen synthase
7
Q
Glycogenin
A
- initiates glycogen synthesis
- glucosyltransferase activity
- contains tyrosine residue (OH group as a nucleophile)
- nucleophilic attack on C1 to displace UDP
- glucose attached to tyrosine residue
- C4-OH attacks C1 of second UDP-glucose to extend the chain
- repeats six times to form an 8 chain glycogen for glycogen synthase activity
8
Q
UDP-Glucose Synthesis
A
- synthesized from glucose-1-phosphate and UTP
- energy comes from Pi hydrolysis
- products are UDP-glucose and pyrophosphate
- UDP-glucose phosphorylase enzyme
- glucose –> glc-6-P –> glc-1-P
9
Q
Glycogen Phosphorylase
A
- uses inorganic phosphate to break 1-4 linkages from non-reducing end
- phosphate cleavage of glycosidic bond
- some energy of the bond conserved in formation of phosphate ester
- acts until it gets 4 residues from a branch bond
- form a favors R state and form b favors T state (phosphorylation promotes transition to R state)
- muscle is b form and liver is a form*
10
Q
De-branching of Glycogen
A
- transferase activity of debranching enzyme:
- moves a block of residues to form a1-4 bond
- breaks a1-4 bond to move 3 residues
- a1-6 glucosidase activity of debranching enzyme:
- a1-6 bond hydrolyzed by adding water to give one free glucose
- product is unbranched chain of a1-4 linked residues for further phosphorylase activity
11
Q
Mechanism of Glycogen Phosphorylase
A
- uses pyridoxal phosphate cofactor in acid/base catalysis and to promote attack of Pi on glycosidic bond
- Schiff base formation
- forms carbanion combining with orthophosphate to form glc-1-p
- HPO4 2- donates proton to the C4 oxygen
12
Q
Fate of Glucose-1-Phosphate
A
- formed from the breakdown of glycogen
- converted to glc-1,6-bisphosphate
- then converted to glc-6-P that can be made into free glucose or used in glycolysis
13
Q
Phosphoglucomutase
A
- contains a phosphorylated serine residue
- phosphorylates C6 of glc-1-phosphate
- dephosphorylates glc-1,6-bisphosphate from C1
14
Q
Regulation of Glycogen Phosphorylase
A
- controlled by phosphorylation
- exists in two forms: phosphorylase a (more active R state) and phosphorylase b (less active T state)
- phosphorylase b kinase phosphorylates the phosphorylase b: stimulates activity/promotes breakdown
- phosphoprotein phosphatase dephosphorylates phosphoylase a: decreases activity/no need for additional breakdown
15
Q
Allosteric Regulation of Glycogen Phosphorylase
A
- in muscle, phosphorylase b is inhibited by ATP and glc-6-P
- in liver, phosphorylase a is inhibited by glucose (shifts equilibrium towards to T, less active, state)
