glycogen metabolsim Flashcards
what is glycogen in the liver used for vs in the muscle?
in liver- used to raise blood glucose, in muscle used locally for mm work
liver glycogen is the main glucose source during-
overnight fast
bonds in glycogen (2)
a1,4- linear
a1,6- branches
MOA of glycogen phosphorylase
uses Pi to cleave a1,4 bonds = glucose-1-p
B6 is a cofactor
MOA of debranching enzyme
at 4 residues away from branch site glycogen phosphorylase will stop and deb ranching enzyme will take over- it was transfer 3 residues to the linear part (4:4 transferase) and it will use a1,6 glucosidase activity to release 1 free glucose
why is it important for glycogen to be branched? (3)
- less osmotically active
- rapid glycogenolysis
- long unbranched polymers are cytotoxic
andersen disease
glycogen storage disease, lack branching enzyme, end up with long glycogen chains, leads to cirrhosis
2 steps of glycogenolysis in mm
glycogen –> glucose-1-P by glycogen phosphorylase
glucose-1-P –> glucose-6-P by phosphoglucomutase
glucose-6-P feeds into glycolysis
3 steps of glycogenolysis in liver
glycogen –> glucose-1-P by glycogen phosphorylase
glucose-1-P –> glucose-6-P by phosphoglucomutase
glucose-6-P –> glucose by glucose-6-phosphatase
glucose enters blood via GLUT2
what happens when epinephrine binds b-adrenergic receptor?
inc cAMP activates PKA activates phosphorylase kinase activates glycogen phosphorylase= inc glycogenolysis= increased blood glucose
what hormones regulate glycogenolysis in liver?
epinephrine
glucagon
what are the covalent modifications that regulate glycogenolysis in liver?
phosphorylase kinase will add P to glycogen phosphorylase to activate it
what is an allosteric inhibitor of glycogen phosphorylase in liver?
high glucose levels = will block glycogenolysis
what are the 3 stimulators of glycogen mobilization in muscle?
epinephrine
mm contraction
nerve impulses via calcium
why does glucagon not act on mm?
mm lacks glucagon receptors
what is required for “full” activation of glycogen phosphorylase?
Ca-calmodulin
phosphorylase kinase-P
what is the unique way that mm regulates glycogenolysis?
muscle contraction leads to increased ADP
adenylate kinase converts ADP to ATP +AMP
AMP will allosterically promote activity of glycogen phosphorylase b (a weaker form of glycogen phosphorylase)
how is an “active glucose unit” formed?
glucose enters cell and is phosphorylated by hexokinase or glucokinase to form glucose-6-P, phosphoglucomutase converts that to glucose-1-P, UDP-pyrophosphorylase converts that to UDP-glucse (active form) and PPi
where is UDP-glucose added to the growing glycogen chain?
non-reducing end
2 enzymes used in glycogen synthesis
glycogen synthase- a1,4- adds 1 glucose in linear fashion branching enzyme (4:6 transferase)- adds 6-7 glucoses to branch
what is glycogenin?
protein that self-glycosylates to form initial glycogen primer, capable of doing this because it has “intrinsic glucosyltransferase activity” that adds UDP-glucose to OH of tyrosine residue, can add total of 8 glucoses
what is the catalyst needed for glycogenin?
Mn2+
what is the inactive form of glycogen synthase?
phosphorylated form
what is the main phosphorylator of glycogen synthase?
glycogen synthase kinase 3 (GSK3)
