Chapter 15: Glycogen Metabolism

Front 1

Glycogen

Back 1

the animal storage form of branched poly(glucose).

Front 2

The process of glycogen breakdown?

Back 2

(glucose)n → glucose-1-phosphate + (glucose)n-1

Front 3

The process of glycogen breakdown?

Back 3

(glucose)n → glucose-1-phosphate + (glucose)n-1

Front 4

Glycogen synthesis

Back 4

(glucose)n-1 + UDP-glucose → (glucose)n

Front 5

Regulation of glycogen breakdown and synthesis is controlled by?

Back 5

2 enzymes, glycogen phosphorylase and glycogen synthase, the activities are activated/inactivated by allosteric regulation and phosphorylation/dephosphorylation

Front 6

Glucogen structure

Back 6

-main chain glucose molecs connected by alpha(1→4) glycosidic bonds
-The branches are attatched by alpha(1→6) glycosidic linkages
-A glucose on the non-reducung ends is cleaved or attatched 1 by 1

Front 7

pathways of Glycogen breakdown

Back 7

In muscle: Glycogen→glucose-6-phosphate(G6P)→glycolosis
In liver: Glycogen→G6P→glucose→ bloodstream→various cells→ glycolysis
-This is because the muscle cells mainly consume glucose molecules whereas the liver cells mainly store the glucose molecules

Front 8

Glycogen breakdown requires what 3 enzymes?

Back 8

-Glycogen phosphorylas, with Pyridoxal phosphate co factor
-Glycogen debranching enzyme
-Phosphoglucomutase

Front 9

Glycogen phosphorylase

Back 9

(glycogen)n+ Pi ↔ (glycogen)n-1 + G1P
-This enzyme releases a glucose unit 1 by 1 until it reaches about 5 units (limit branch) from a branch point
- the enzyme has a crevice where 4-5 units of a left handed helical glycogen can fit, but its too narrow to fit a branch point

Front 10

Enzyme-catalyzed modification/ demodification process yields ? forms of phosphorylase

Back 10

2
Phosphorylase a: E-O-PO (attatched at Ser-14)
Phosphorylase b: no phosphate attaachment
Both forms are are allosterically activated or inactivated

Front 11

Allosteric Inhibitors?

Allosteric Activators?

Back 11

Inhibitors: ATP,G6P,Glucose

Activators: AMP, [F2,6P]

Front 12

? is an essential cofactor for phosphorylase

Back 12

Pyridoxal phosphate (PLP)
-PLP covallently bound to phosphorlase via Schiff base to Lys-679

-PLP's phosphate group probably functions as an acid-base catalyst

Front 13

Glycogen debranching enzyme

Back 13

removes branches so that glycogen phosphorlase can complete reaction

Front 14

Phosphoglucomutase

Back 14

-Catalyzes the conversion of G1P to G6P
-G1P produced from the glycogen breakdown must be converted to G6P in order to enter glycolysis or to produce glucose in liver
-The Ser of the enzyme is phophorylated

Front 15

Glycogen Synthesis

Back 15

A. UDP-glucose formation by UDP-glucose pyrophosphorylase
B. Glycogen synthesis by glycogen synthase
C. Glycogen Branching

Front 16

UDP-glucose formation by UDP-glucose pyrophosphorylase

Back 16

-in the glycogen synthesis pathway, at first, the uridine diphosphate (UDP) is attatched to glucose
-This reaction is catalyzed by UDP-glucose pyrophosphorylase

Front 17

Glycogen synthesis by glycogen synthase

Back 17

1. The glycosidic bond between glucose and UDP in UDP-glucose is hydrolyzed. The cleaved glucose ion takes on the oxonium ion intermediate (1/2 chair conformation), stabilized by the enzyme
2. The glucose unit of UDP-glucose is transferred to the C4-OH group on one of glycogen's non-reducing ends to form an alpha(1-4) glycosidic bond.

Front 18

Thermodynamics of glycogen synthesis by glycogen synthase

(glucose)n->G1P +(glucose)n-1

Back 18

∆G of glycogen breakdown by glycogen phosphorylase is less than 0, about -5 to -8 kj/mol

Front 19

∆G of glycogen synthesis by glycogen synthase

Back 19

about -14 kj/mol
(glucose)n-1+UDP-glucose ->(glucose)n

Front 20

Both reactions are?

Back 20

spontaneous under the same physiological conditions
- but glycogen synthesis uses one ATP hydrolysis per glucose for energy source

Front 21

Glycogen Branching

Back 21

about 7 units of the non-reducing end of alpha-amylose chain are removed at alpha(1-4)linkage, and reattatched to the C6 of the other alpha-amylose chain by alpha(1-6)linkage
-the transfer is carried out by amylo-(1,4->1,6)-transglycosylase (branching enzyme)

Front 22

∆G of hydrolysis of alpha(1->4) glycosidic bond?

Back 22

-15.5 kj/mol

Front 23

∆G of hydrolysis of alpha (1->6) glycosidic bond

Back 23

+7.1 kj/mol

Front 24

Control of glycogen metabolism
A: Allosteric control of glycogen phosphorylase and glycogen synthase

Back 24

Glycogen phosphorylase- has two forms (a and b), and each form is activated allosterically from T-form to R-form

Front 25

Phosphorylase b

Back 25

non-phosphorylated enzyme and its R-form is less active
-but it's response is fast because it's activation signal(activators) come from inside the cell.

Front 26

Phosphorylase a

Back 26

The Ser-14 phosphorylated enzyme and it's R-form is the most active enzyme
-resonse is slow since its activation signals (effectors) come from the outside of the cell

Front 27

Phosphorylase kinase and phosphoprotein phosphatase

Back 27

Phosphorylates and dephosphorylate the enzyme, this is called covalent modification
-they are enzyme modificator and demodificator respectively
Unmodified form (phosphorylase b) is mostly T-form, whereas modifie form (phosphorylase a) is mostly R-form

Front 28

At high demand for ATP ie low ATP, low G6P, and high AMP?

Back 28

Glycogen phosphorylase is stimulated and glycogen synthase is inhibited, so flux through this pathway favors the glycogen breakdown

Front 29

At high ATP and G6P

Back 29

Glycogen synthasis is favored

Front 30

what is the most effective activatin process of phosphorylase?

Back 30

Phosphorylation

Front 31

Enzyme cascades

Back 31

when one molecule of enzyme can produce a many product through a series of reactions