Glycogen metabolism Flashcards
What is the structure of a glycogen molecule?
Glycogen chains extend in tiers, each chain has 12-14 glucose residues, there is branch points every 8-12 residues
What are the five ways enzymes can be regulated/
availability of substrates and cofactors sequestering being associated with a regulatory protein covelnet modification phosphorylation allosteric enzymes
Which amino acids are phosphorylated?
Tyr, Ser, Thr, ie. those that have a hydroxyl group attached
Also His
How can phosphorylation regulate an enzyme?
1) can change enzyme conformation to a more or less active state
2) affect substrate binding affinity
How do allosteric enzymes differ from enzymes that follow standard Michaelis-Lenten kinetics?
Allosteric enzymes are usually made up of more than one domain. Catalytic unit and a regulatory unit, sigmoid graph
How does a positive and negative effector change the kinetics of the enzyme?
affects the binding affinity or the speed of activity or both
What is the differemce between a V-type and K-type effector?
V-type changes the speed of activity, K-type changes the binding affinity
What happens to the shape of the graph for a V-type and K-type effector in the presence of a negative effector?
V: shifts down
K: shifts right
What happens to the shape of the graph for a V-type and K-type effector in the presence of a positive effector?
V;shifts up
K:shifts left
Which enzymes and transporter are activated in the cell signaling cascade by insulin?
PP-1 and GLUT 4 in muscle
What role does PP1 play in glucose metabolism?
F2,6BP is a positive allosteric effector for PFK-1 in glycolysis. PFK-2/F26BPase is a bifunctional enzyme responsible for making this, least the kinase part is. This enzyme is active when it is dephosphorylated. Therein insulin activated PP1, which dephosphorylates the bifunctional enzyme, which makes F2,6BP, which allosterically favors glycolysis.
F2,6BPase and PFK-2 are bifunctional enzymes. Which part is activated upon phosphorylation?
F2,6BPase (PFK-2 inhibited)
PKA phosphorylates the dual functional enzyme.
F2,6BPase removes the extra P from F2,6Bp making is F6P.
This cannot activate PFK-1, and can no longer inhibit FBPase-1. Gluconeogenesis occurs.
What are positive effectors for PFK-1
AMP, ADP, F2,6BP
What are negative effectors for PFK-1
citrate, ATP, means energy levels are high and TCA intermediates are high and glucose shoudl not be degraded
What are the enzymes responsible for the breakdown of glycogen?
glycogen phosphorylase - G1Ps
debranching enzyme - transferase (three Gs are removed from a branch point and added to a linear chain) and glucosidase (cuts off the G at the branch, just plain G)
phosphoglucomutase - shifts P from 1 to 6, can enter glycolysis directly in muscle
glucose-6-phosphotase - in liver only so it can send free G into the blood stream
What is the role of UDP-sugar pyrophosphorylase? Why is this step necessary?
Adds a UtP to G1P. This nucleotide R group on the sugar will provide a hi energy relesae when it is broken, favoring the joining of two sugars. It also helps with noncovalent interactions in the binding site. Also tags it for glycoen synthesis.
How is the primer synthesized?
Glycogenin adds a UDP-glucose to one of its Tyr residues (Tyr 194). This is repeated until there is a chain of 8 G.
What are the enymes responsible for making glycogen?
glycogen synthase
UDP-pyrophosphorylase - attaches UTP to G1P
glycosyl 4,6 transferase - takes a branch of 6-7 G and puts them else where to make a branch (must be 11 there before you take the 6-7 away)
phosphoglucomutase - backing it up to G1P from G6P so the nucleotide can be added
positive Regulation of glycogen synthase
insulin, PP1, GS needs to be DE phosphorylated to work
insulin, PKB, inactivates (by phosphorylation) GSK-3, which would phosphorylate and inhibit GS if it could
negative regulation of glycogen synthase
glucagon, PKA, does two things, phosphorylates PP1, inactivating it and
phosphorylates GS
Also GSK-3 phosphorylates GS. Not sure which one is more important tho
allosteric, glucose, GP
glucose is a negative allosteric effector for glycogen phosphorylase
allosteric, glucose, glucose 6 P, GS
glucose and glucose 6 phosphate are positive allosteric effectors of glycogen synthase
active PKA inhibits
PP1, this is how GP stays phosphorylated and GS also stays phosphorylated (inactivated)
Does PKA (cAMP dependent protein kinase) directly change Glycogen Phosphorylase?
NO! It phosphoryalte glycogen phosphorylase b kinase, which is the activator of GP.
