lecture 9: glycogenolysis

if glucose is synthesized at night, it will be stored as ____________

glycogen

recall: glycogen is the readily metabolized ________________ of glucose

storage form

glycogen is a branched homopolymers of glucose with what types of linkages?

alpha (1,4) with alpha (1,6) branches

glucose can be added or removed from the ______________ of glycogen

non-reducing ends

non-reducing ends of the glycogen = _______

free 4' -OH

thus, the ___________ in glycogen give more ends to either add (or remove) glucose to/from

branches

in the liver, what is the function of glycogen?

the synthesis and breakdown of glycogen is regulated to maintain blood glucose levels (using insulin and glucagon)

in the muscle, what is the function of glycogen?

the synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cell

when blood glucose levels _______, glycogen will be broken down to release glucose units

fall

glycogen breakdown

glycogenolysis

glycogenolysis is a ________ process

catabolic

what three enzymes are required for glycogenolysis?

1. glycogen phosphorylase

2. phosphoglucomutase

3. glycogen debranching enzyme

glycogen phosphorylase

glycogen + Pi --> glucose 1 phosphate + glycogen (n-1)

glycogen phosphorylase cleaves the _____________

alpha (1-4) linkages

glycogen phosphorylase is a phosphoryLASE not a _________

Phosphatase

a phosphorylase enzyme does what?

uses Pi to attack (get a phosphorylated product)

a phosphatase enzyme does what?

uses water to attack (to remove a phosphate)

if you attack glycogen with water (phosphatase), you would get ________ (instead of G1P)

glucose

you would then need to use ATP to phosphorylate glucose to G6P in glycolysis which ___________

costs energy

but, since you attack glycogen with Pi you already get a ______________ product

phosphorylated

thus, you only need to isomerize G1P into ___________ which saves energy

G6P

Phosphorylase yields G1P which is charged, meaning what?

it gets trapped inside the cell

glycogen phosphorylase enzyme requires what vitamin cofactor?

peridoxical phosphate (PLP)

PLP is derived from __________

Pyridoxine (vitamin B6)

note: PLP acts as a _________ and ________ in the reaction

proton donor and acceptor

phosphate of PLP participates in acid/base _________________

catabolism

also hydrophobic ring of PLP helps _______________________

keep water out of the active site of the enzyme (and keep Pi in)

note: PLP is also required cofactor for enzyme in ____________ metabolism

amino acid

glycogen phosphorylase is a ________ enzyme

processive

processive meaning that it slides along the glycogen polymer, cleaving off residues without having to __________ and ________ after each reaction

dissociate and rebind

processive enzymes are much more ________ in this way

efficient

what other enzymes in biology are processive enzymes that we have learned about previously?

DNA and RNA polymerase

which enzyme catalyzes the conversion from G1P to G6P?

phosphoglucomutase

glycogen phosphorylase releases G1P but we need G6P to enter into __________

glycolysis

Note: G6P can bypass the first _________ reaction of glycolysis and go straight into the second reaction

hexokinase

glycogen phosphorylase cleaves only at ____________ and not __________

alpha (1-4) linkages and not alpha (1-6 linkages)

in fact, glycogen phosphorylase will stop ____ residues before it reaches a branch point

4

so how are branches removed from glycogen?

glycogen debranching enzyme

glycogen phosphorylase will stop __________ away from a branch point

4 residues

glycogen debranching enzyme shifts _________________ from one strand to another (transferase activity)

3 glycosyl units

then, it _________ the remaining alpha(1-6) sugar (glucosidase activity)

hydrolyzes

the _________ and ____________ activities of glycogen deb ranching enzyme are separate enzymes in some bacteria like E. coli

transferase and glucosidase

in the liver, what is the goal for glycogen breakdown?

release free glucose into the blood

in the liver, G1P --> G6P --> glucose and it can make the glucose from G6P with what specific enzyme that the liver only has?

glucose 6 phosphatase (removes a phosphate)

in the muscle, what is the goal for glycogen breakdown?

use G6P for energy for itself

in the muscle, G1P --> G6P --> ___________

glycolysis

the liver can release free glucose to the blood to be taken up by the _________ and active muscle

brain

the liver regulates what?

blood glucose levels

recall, the muscle does not have _____________

G6P phosphatase

the muscle therefore retains the G6P to be used for its own energy since the phosphorylated glucose is __________________ and without G6P phosphatase, it can't convert it back to free glucose so it can't be released

trapped inside the cell