Glycogen metabolism

Question 1

What is the structure of a glycogen molecule?

Answer 1

Glycogen chains extend in tiers, each chain has 12-14 glucose residues, there is branch points every 8-12 residues

Question 2

What are the five ways enzymes can be regulated/

Answer 2

availability of substrates and cofactors
sequestering
being associated with a regulatory protein
covelnet modification
phosphorylation
allosteric enzymes

Question 3

Which amino acids are phosphorylated?

Answer 3

Tyr, Ser, Thr, ie. those that have a hydroxyl group attached

Also His

Question 4

How can phosphorylation regulate an enzyme?

Answer 4

1) can change enzyme conformation to a more or less active state
2) affect substrate binding affinity

Question 5

How do allosteric enzymes differ from enzymes that follow standard Michaelis-Lenten kinetics?

Answer 5

Allosteric enzymes are usually made up of more than one domain. Catalytic unit and a regulatory unit, sigmoid graph

Question 6

How does a positive and negative effector change the kinetics of the enzyme?

Answer 6

affects the binding affinity or the speed of activity or both

Question 7

What is the differemce between a V-type and K-type effector?

Answer 7

V-type changes the speed of activity, K-type changes the binding affinity

Question 8

What happens to the shape of the graph for a V-type and K-type effector in the presence of a negative effector?

Answer 8

V: shifts down
K: shifts right

Question 9

What happens to the shape of the graph for a V-type and K-type effector in the presence of a positive effector?

Answer 9

V;shifts up

K:shifts left

Question 10

Which enzymes and transporter are activated in the cell signaling cascade by insulin?

Answer 10

PP-1 and GLUT 4 in muscle

Question 11

What role does PP1 play in glucose metabolism?

Answer 11

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.

Question 12

F2,6BPase and PFK-2 are bifunctional enzymes. Which part is activated upon phosphorylation?

Answer 12

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.

Question 13

What are positive effectors for PFK-1

Answer 13

AMP, ADP, F2,6BP

Question 14

What are negative effectors for PFK-1

Answer 14

citrate, ATP, means energy levels are high and TCA intermediates are high and glucose shoudl not be degraded

Question 15

What are the enzymes responsible for the breakdown of glycogen?

Answer 15

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

Question 16

What is the role of UDP-sugar pyrophosphorylase? Why is this step necessary?

Answer 16

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.

Question 17

How is the primer synthesized?

Answer 17

Glycogenin adds a UDP-glucose to one of its Tyr residues (Tyr 194). This is repeated until there is a chain of 8 G.

Question 18

What are the enymes responsible for making glycogen?

Answer 18

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

Question 19

positive Regulation of glycogen synthase

Answer 19

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

Question 20

negative regulation of glycogen synthase

Answer 20

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

Question 21

allosteric, glucose, GP

Answer 21

glucose is a negative allosteric effector for glycogen phosphorylase

Question 22

allosteric, glucose, glucose 6 P, GS

Answer 22

glucose and glucose 6 phosphate are positive allosteric effectors of glycogen synthase

Question 23

active PKA inhibits

Answer 23

PP1, this is how GP stays phosphorylated and GS also stays phosphorylated (inactivated)

Question 24

Does PKA (cAMP dependent protein kinase) directly change Glycogen Phosphorylase?

Answer 24

NO! It phosphoryalte glycogen phosphorylase b kinase, which is the activator of GP.

Question 25

In regards to glycogen phosphorylase, what does PKA do?

Answer 25

activates glycogen phosphorylase b kinase

phosphorylates and inactivates PP1

Question 26

Does PP1 have an intermediat enzyme to act upon GP?

Answer 26

NO, directly dephosphorylates GP