BCH 400 Glycogen Metabolism

Includes chapter 24: glycogen degradation & chapter 25: glycogen synthesis

What is glycogen's main role?

Glucose storage

Which two linkages form glycogen?

α(1→4) and α(1→6)

Which linkage forms the linear glycogen chains?

α(1→4)

Which linkage forms glycogen branches?

α(1→6)

About how often are glycogen branches found?

Every 7–10 residues

How does branching affect glucose release?

More nonreducing ends

From which ends is glycogen broken down?

Nonreducing ends

Why are glycogen synthesis and breakdown separate pathways?

Avoid futile cycling

What are the three stages of glycogen breakdown?

Release, rearrange, convert

What enzyme releases glucose-1-phosphate from glycogen?

Glycogen phosphorylase

What is the main product of glycogen phosphorylase?

Glucose-1-phosphate

What type of reaction does glycogen phosphorylase catalyze?

Phosphorolysis

What molecule cleaves glycogen during phosphorolysis?

Orthophosphate

Does glycogen phosphorylase use ATP for cleavage?

No

Which glycogen bond does phosphorylase cleave?

α(1→4)

How close to a branch point does phosphorylase stop?

Five residues away

Which enzyme processes glycogen branch points?

Debranching enzyme (GDE)

What does GDE transfer from a branch?

Trisaccharide

Where does GDE transfer the trisaccharide?

Adjacent α(1→4) chain

What remains at the α(1→6) branch point?

One glucose

How is the remaining branch-point glucose released?

Hydrolysis

What are the products of glycogen breakdown?

G1P and glucose

Which glycogen breakdown product is most abundant?

G1P

Which enzyme converts G1P into G6P?

Phosphoglucomutase

Is the phosphoglucomutase reaction reversible?

Yes

What enzyme can convert free glucose into G6P?

Hexokinase or glucokinase

Which enzyme releases free glucose from G6P in liver and kidney?

Glucose-6-phosphatase

What are the two broad types of glycogen regulation?

Allosteric and covalent

Which two enzymes are central to glycogen regulation?

Phosphorylase and synthase

What are the two covalent forms of glycogen phosphorylase?

GPa and GPb

Which glycogen phosphorylase form is more active?

GPa

Which glycogen phosphorylase form is less active?

GPb

What converts GPb into GPa?

Phosphorylation

Which enzyme phosphorylates GPb?

Phosphorylase kinase

Which residue is phosphorylated on GPb?

Serine 14

Which enzyme transfers phosphate from ATP to GPb?

Phosphorylase kinase

How many ATP molecules are used per GPb conversion?

Two ATP

Which allosteric molecule activates GPb?

AMP

What conformational change does AMP cause in GPb?

T state to R state

Which molecules inhibit GPb allosterically?

ATP and G6P

What does high ATP signal to GPb?

High energy

What does high AMP signal to GPb?

Low energy

What conformational state is more active?

R state

What conformational state is less active?

T state

What does glucose do to GPa?

R state to T state

Which tissue's phosphorylase responds to glucose?

Liver

Is liver glycogen phosphorylase sensitive to AMP?

No

What activates phosphorylase kinase besides phosphorylation?

Calcium

Which subunit binds calcium in phosphorylase kinase?

Calmodulin

Which kinase phosphorylates phosphorylase kinase?

Protein kinase A (PKA)

Which second messenger activates PKA?

cAMP

Which enzyme produces cAMP?

Adenylate cyclase

What activates adenylate cyclase?

G protein

What type of receptor activates the G protein?

7-TM receptor

What is another name for a 7-TM receptor?

GPCR

Which hormone binds the β-adrenergic receptor?

Epinephrine

Which hormone preferentially stimulates liver glycogen breakdown?

Glucagon

Which hormone has its greatest effect on muscle glycogen breakdown?

Epinephrine

What is the signaling sequence after hormone binding?

G protein → cyclase → cAMP

Which kinase is activated by cAMP?

PKA

What does PKA phosphorylate in glycogen breakdown?

Phosphorylase kinase

What does phosphorylase kinase then phosphorylate?

GPb

What is the net effect of this cascade?

Glycogen breakdown

How do G proteins turn themselves off?

GTP hydrolysis

What does GTP hydrolysis produce on the G protein?

GDP

Which enzyme breaks down cAMP?

Phosphodiesterase

What does phosphodiesterase produce from cAMP?

AMP

Which substance inhibits phosphodiesterase?

Caffeine

Which phosphatase removes phosphate from glycogen enzymes?

Phosphoprotein phosphatase (PP-1)

What happens to phosphorylase kinase after PP-1 acts?

Inactivated

What happens to GPa after PP-1 acts?

Converted to GPb

Which hormone activates PP-1?

Insulin

What happens to PP-1 inhibitor PI-1 after PKA phosphorylation?

It inhibits PP-1

What happens to PI-1 after dephosphorylation?

Stops inhibiting PP-1

Which protein binds PP-1 in the liver regulatory mechanism?

GL

What does glucose binding to GPa promote in liver?

GPa release from GL

What is the effect of GPa release from GL?

PP-1 activation

What are the two forms of glycogen synthase?

GSa and GSb

Which glycogen synthase form is more active?

GSa

Which glycogen synthase form is less active?

GSb

What does phosphorylation do to glycogen synthase?

Decreases activity

Which kinase phosphorylates GSa in the textbook pathway?

PKA

What does PKA convert GSa into?

GSb

Which molecule allosterically activates GSb?

G6P

What happens to glycogen synthase after PP-1 acts?

Activated

What is reciprocal regulation?

Opposing pathway control

What does reciprocal regulation prevent?

Futile cycling

What happens to phosphorylase after phosphorylation?

Activity increases

What happens to synthase after phosphorylation?

Activity decreases

What happens to phosphorylase after dephosphorylation?

Activity decreases

What happens to synthase after dephosphorylation?

Activity increases

What is the overall effect of epinephrine or glucagon?

Breakdown on; synthesis off

What is the overall effect of insulin?

Synthesis on; breakdown off

What is glycogen synthesis also called?

Glycogenesis

What is glycogen breakdown also called?

Glycogenolysis

What molecule begins glycogen synthesis?

Glucose-1-phosphate

What nucleotide triphosphate activates glucose for glycogen synthesis?

UTP

Which enzyme forms UDP-glucose?

UDP-glucose pyrophosphorylase

What is the activated glucose intermediate in glycogenesis?

UDP-glucose

What is the energy source for UDP-glucose formation?

UTP