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Flashcards in Glycogen Metabolism Deck (19):
1

Glycogenolysis: Phosphoglucomutase

Type of Enzyme?

•Active site contains___________ residue

•Reaction proceeds via intermediate, ___________

Isomerase

phosphoserine

Glu-1,6-bisP

2

Glycogenolysis (glycogen breakdown)

•Glycogen phosphorylase

–Cannot approach any closer than _________ residues from a branch point

•Debranching enzyme:

–Transferase: shifts block of 3 ______ units

–α-1,6-glucosidase: hydrolyzes branch point, generating ____

•Glucose converted to Glu6P via ________

•4th activity: phosphoglucomutase

4

glucose

glucose

hexokinase

3

      Glycogenesis: Other Enzymes Involved        

•Branching enzyme catalyzes the formation of a-1,6 glycosidic linkages in glycogen by transferring a block of about 7 residues to a more interior location.

•New branchpoint must be at least ________ residues from preexisting one

•Branching increases the _______ of glycogen and facilitates both its synthesis and its degradation

•Addition of one glucose residue to glycogen uses ___________ ATP equivalents.

 

4

solubility

two

4

Glycogen synthesis requires the protein Glycogenin (G)

•Glycogenin

–acts as both an initial primer and an _______

–First, transfers glucose from ________ to hydroxyl of __________ on protein

–Next, extends chain by addition of _______ more residues

•________(and branching enzyme) then takes over

•Glycogenin remains buried within the b-particle, attached to the single__________ end

enzyme

UDP-glucose;tyrosine

7

Glycogen synthase

reducing

5

Glycogenolysis: Glycogen Phosphorylase

•Carries out ___________ (cleavage of a bond using ______________)

–Energetically favorable; product already phosphorylated

–Glu1P, being charged, remains inside ________ cell and is used for energy; in liver, Glu1P converted to glucose and secreted

–Requires _______________PLP) as cofactor

 

phosphorolysis;orthophosphate, Pi

muscle

pyridoxal phosphate 

6

Glycogenesis (Glycogen Synthesis): _________ is the substrate for glycogen synthase

*Note that subsequent hydrolysis of___________- drives the reaction forward

UDP-glucose

pyrophosphate (PPi)

7

Glycogen

•A readily-mobilizable storage form of __________

•Found in two places in body:

_____________

________________

•Present in granules called ____________

–Contain _________ that degrade, synthesize and regulate glycogen

glucose

–liver 

-muscle 

“b-particles”

enzymes

8

          Hormonal Control of Glycogen Metabolism

•How would you expect low blood glucose level to affect glycogenesis? How are low blood glucose levels achieved in the liver and muscle?

•How would you expect high blood glucose level to affect glycogenesis? 

 

Low blood glucose level, through the action of glucagon (liver) or epinephrine (liver, muscle) inhibits glycogenesis and stimulates glycogenolysis.

–High blood glucose level, through the action of insulin, stimulates glycogenesis and inhibits glycogenolysis in liver and muscle. 

9

The Epinephrine (or Glucagon)-Triggered Signaling Cascade by which Phosphorylase is Activated

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10

T-to-R Transition of Muscle (and Liver) GPPase Responsive to Cellular Conditions

•MUSCLE: GPPase “b” usually inactive, because levels of allosteric inhibitors (_________ and ________) usually high

•GPPase “b” is only active when level of __________ is high.

–Therefore, GPPase ________ is responsive to energy charge

–Here, AMP is “plugging the gap” until the hormone ________ can take over and convert “b” to “a”

•But GPPase _______ nearly always “on”—or active

•LIVER: default state is ________ form, which is allo-sterically inhibited by ________.

–Insensitive to AMP

ATP, Glu6P

AMP

“b”

epinephrine

"a"

“a”

glucose

11

Glycogen: A large,___________ polymer of glucose

•residues connected by _________ o-glycosidic bonds with a-1,6 branch points every ~10 residues

•> 20,000 non-reducing ends per b-particle

–Targets of glycogen phosphorylase-catalyzed removal of glucose

•Only one reducing end—it is attached to the protein ____________

branched

a-1,4; a-1,6

glycogenin

12

Hormonal Control of Glycogen Metabolism: After a Meal or at Rest

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13

Regulation of Muscle Glycogen Phosphorylase Activity

•Highly regulated both allosterically (_______-form) and by reversible covalent modification (___________)

–Allosteric inhibitors: ________ and ________; activator: _______

•Phosphorylation is under ___________ control

•Exists in two interconvertible forms

–GPPase “a”: phosphorylated, usually active, in _______-state

–“b”: unphosphorylated, usually inactive, in ________-state

–GPPase “b” converted to “a” via phosphorylation of single __________ residue on each subunit

•Enzyme: ____________

“b”; phosphorylation

ATP, Glu6P

AMP

hormonal

R

T

serine

Phosphorylase kinase

14

Fates of Glucose 6-Phosphate derived from Glycogen

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15

Phosphorylase b Kinase is Itself Regulated (in muscle)

•Partially activated by either _______or ________ binding but fully activated when both involved

–Ca2+ levels rise in muscle cell during muscle _________

•Phosphorylation site is on _______subunit

•Ca2+ binds to ________subunit (also known as ______)

phosphorylation; Ca2+

contraction

b

d ; calmodulin

16

Hormonal Regulation of Phosphoprotein Phosphatase-1 (PP1) in Liver

•High glucose levels activate glycogenesis

•Binding of glucose to GPPase causes an R-to-T shift, dissociation of GPPase, and _________ of PPI, allowing it to _______ GPPase and GS

•“glucose sensor”

activation;dephosphorylate

17

Overview of Glycogen Metabolism

•Breakdown involves 4 enzymatic activities

–Release of glucose 1-phosphate (from NR ends. Enzyme: _____________

–Remodeling to remove branchpoints. Enzyme (s):_________

–Conversion of Glu1P to Glu6P. Enzyme: __________

•Synthesis involves

–Glycogen synthase: uses ___________ as substrate

–Branching enzyme: creates a-1,6 branchpoints

•The two processes reciprocally regulated; different enzymes, different substrates/products

glycogen phosphorylase

transferase and glucosidase

 phosphoglucomutase

UDP-glucose

18

Hormonal Regulation of Phosphoprotein Phosphatase-1 (PP1) in Muscle

•PP1 is tightly bound to a “glycogen-targeting protein,” GM, which forms a complex with the 3 enzymes GS, GPPase and phosphorylase kinase

•1) PP1 becomes __________when GM is singly phosphorylated (by ISK), but 2) double-phosphorylation of GM (by PKA) leads to its _________

Activated; inhibition

19

In liver, insulin activates Glycogen Synthase by inactivating ___________

•Glycogen synthase is major regulatory enzyme of __________

•Exists in two states: active, “a” (unphosphorylated) and inactive, “b” (phosphorylated)

•Can be phosphorylated on various _____residues 

•Action of GSK3 opposed by _______and ______

Glycogen Synthase Kinase-3

glycogenesis

serine

Phosphoprotein Phosphatase-1 ; insulin