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MC Biochem 2 > Chpt 21: Glycogen Metabolism > Flashcards

Chpt 21: Glycogen Metabolism Flashcards

1
Q

Glycogen Anabolism

A

stores glucose

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2
Q

Glycogen Catabolism

A

Breakdown/releases glucose

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3
Q

Sources of glucose

A
  • Diet
  • Degradation of glycogen
  • Gluconeogenesis
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4
Q

Glycogen

A

1) is a branched-chain homopolysaccharide made from alpha-D-glucose
- alpha 1,4 glycosidic bonds
- alpha 1,6 glycosidic brances
* branching increases solubility of glycogen

2) ready supply of glucose
- liver glycogen provides glucose to blood
- Skeletal muscle glycogen provides energy for muscle contraction

3) Glycogen storage
- increases during well-fed state
- depleted during fasting state

4) stored in cytoplasm

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5
Q

Breakdown of Glycogen

A

1) Glycogen (x) + orthophosphate (Pi) -> Glycogen (x-1) + glucose 1-Phosphate catalyzed by glycogen phosphorylase and continues until its 4 glucose residues from alpha 1,6-branch
2) Glycogen (4 residues from branch)-> Glycogen (x+3) catalyzed by Oligo-alpha (1-4)-alpha(1-6)-glucan transferase
- transfers 3 glucose residues from branch to main chain
3) Glycogen (x-1) with final branch residue-> Glycogen (x-1) + glucose (free) catalyzed by Amylo alpha-(1-6) glucosidase
- Hydrolysis reaction OTHER REACTIONS ARE PHOSPHOROLYSIS REACTIONS

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6
Q

Debranching enzymes

A

Bifunctional Enzyme

1) Oligo-alpha(1-4)-a(1-6)-glucan transferase
- transfers 3-4 residues at branch to another chain thus lengthening the “other” chain by 3-4 residues
2) Amylo-alpha(1-6) glucosidase
- releases free glucose from residue at Alpha 1,6 branch via HYDROLYSIS (ADDITION OF WATER)

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7
Q

Liver vs Muscle Glycogen Metabolism

A

Liver cells (hepatocytes) contains Glucose 6-phosphatase which provides free glucose for cell (distribution via blood)

Muscles Cells lack glucose 6-Phosphatase so the Glucose 6-Phosphate enters glycolysis to provide ATP for muscle contraction

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8
Q

Liver specific glycogen catabolism

A

1) Glycogen(x) + Pi -> Glycogen (x-1) + Glucose 1-Phosphate via glycogen phosphorylase
2) Glucose 1-Phosphate -> Glucose 6-Phosphate (cytosol) catalyzed via phosphoglucomutase (cytosol)
3) Glucose 6-Phosphate (cytosol)-> Glucose 6-Phosphate (lumen of ER) via Glucose 6-Phosphate translocase
4) Glucose 6-Phosphate (lumen of ER)-> Glucose (blood) via Glucose 6-Phosphatase (ER)

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9
Q

Glycogen Phosphorylase

-structure

A

Homodimer

1) N-terminal domain:
- Glycogen binding site
- Catalytic site between the two domain
2) C-terminal domain

PLP-pyridoxal Phosphate- Prosthetic group

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10
Q

Glycogen Phosphorylase

-function

A

Catalyzes the sequential removal of Glucose 1-Phosphate from nonreducing end of glycogen via Phosphorylysis until it reaches 4 residues from branch then requires debranching enzymes
-Not hydrolysis-water excluded from active site

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11
Q

PLP

A

Pyridoxal Phosphate

Prosthetic Group of Glycogen Phosphorylase
-attached to lysine of enzyme through Schiff’s base

Function:

  • Group transfer to or from amino acids
  • Proton donor/acceptor

Vit-Pyridoxine (B6)

Deficiency:
-Depression, Confusion, Convulsion

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12
Q

Glycogen Phosphorylase Regulation

A

Regulation:

1) Allosteric- Tissue Specific
- Liver
- Muscle
* different in liver and muscle due to different effectors
2) Reversible Phosphorylation-Hydroxyl of Ser
- a form=phosphorylated
- b form=dephosphorylated
3) Calcium
- only in muscle
- release of calcium triggers contraction from sarcoplasmic reticulum

Alternate between Two Forms:

1) Phosphorylase A:
- active form
- may exist in either T or R state
2) Phosphorylase B:
- inactive form
- May exist in either T or R state

Liver and muscle cells differ in response to Inhibitors:
-Isozymes~90% identical

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13
Q

T and R state of Phosphorylase

A

Each form (a and b) exists in equilibrium of one of two states:

1) Tight (T) state
- inactive form
- favored by Phosphorylase b (dephosphorylated form)
2) Relaxed (R) state
- active form
- favored by Phosphorylase a (Phosphorylated form)

Phosphorylation of Ser converts B to A

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14
Q

Allosteric Regulation of Muscle Glycogen Phosphorylase

A

Muscle Glycogen Phosphorylase releases Glucose 6-Phosphate for use by the muscle cell for production of ATP to power contraction

  • Resting muscles contain mostly Phosphorylase B
  • exercise stimulates conversion of phosphorylase B->A by phosphorylating OH of serine

Muscle Phosphorylase A:

  • Hormonal Signals stimulates phosphorylation of B-> A by a phosphorylase kinase
  • always active:
    1) release glucose to synthesize ATP for muscle contraction
    2) independent of [AMP], [ATP], [G6P]
Muscle Phosphorylase B:
1)Stimulated by:
High [AMP] increases activity
-binds to nucleotide binding site
-release glucose to produce ATP
Indirectly High [Ca2+] increases activity
2)Inhibited By High Energy Charge:
High [ATP] decreases activity 
-competes with AMP for nucleotide binding site
High [G6P] decreases activity
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15
Q

Allosteric Regulation Liver Glycogen Phosphorylase

A

Liver Glycogen Phosphorylase functions to release glucose from the liver for transport to other tissue via blood

High glucose concentration decreases activity:
-If blood glucose is high then glycogen catabolism is not needed to produce free glucose

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16
Q

Hormonal Regulation:

-Liver and Muscles

A

Glucagon (to a lesser extent epinephrine (adrenaline))
-Liver-stimulates glycogen catabolism-release of glucose in blood

Epinephrine (adrenaline)
-Muscle-stimulates glycogen catabolism-release of glucose for glycolysis

17
Q

Epinephrine (Adrenaline)

A

1) Catecholamine derived of tyrosine
2) Synthesized in adrenal medulla
- located in adrenal glands on top of kidney
3) Released in response to low blood glucose concentration
4) Stimulates catabolism of glycogen in muscles (and lesser extent in liver)
- In muscles bind to B-adrenergic receptor
- in liver binds to:
a) B-adrenergic receptor
b) A-adrenergic receptor-Phosphoinositide cascade which stimulates Ca2+ release

18
Q

Glucagon

A

Peptide Hormone

  • Secreted by alpha cells of pancreas
  • Released in response to low blood glucose concentration (starved state)
  • Stimulates catabolism of glycogen in liver by binding to glucagon receptor
19
Q

Glycogen Phosphorylase Signal Transduction Pathway

A

1) Epinephrine (Muscle) or Glucagon (Liver) binds to 7TM receptor(B-adrenergic receptor) which stimulates activation of 100 G proteins
2) Active G protein binds to and activates Adenylate Cyclase
3) Adenylate Cyclase synthesizes cAMP using ATP as substrate (alot of ATP used)
4) cAMP activates Protein Kinase A by binding to the Regulatory Subunit
5) Protein Kinase A phosphorylates Phosphorylase Kinase (active)
6) Phosphorylase Kinase phosphorylates OH of Ser on glycogen Phosphorylase which converted B-> A (TURNED ON)

20
Q

7TM Receptor

-function/structure

A 
Seven Transmembrane-helix receptor
50% of therapeutic drugs target this class of receptors
-B adrengernic receptors are members of this class

7 Membrane spanning alpha helixes

Binding of hormone stimulates activated of G proteins
-1 receptor activates 100s of G proteins

21
Q

G Protein

-function/structure

A

Heterotrimeric protein binds guanyl nucleotides

Heterotrimer:
-Ga(alpha subunit)-nucleotide binding subunit, in active/stimulated form it binds to adenylate cyclase
a) Inactive form bound to GDP
b) Active form bound to GTP
c) Member of P-loop ATPase family
Gby (beta/gamma subunit)-exchanges GDP for GTP on alpha subunit

22
Q

Adenylate Cyclase

-function

A

Amplifies signal of hormone by synthesizing cAMP

23
Q

Protein Kinase A

  • structure
  • function
A

Heterotetramer of two subunits-R2C2

1) catalytic (C) subunit
- Phosphorylates target protein when freed from R subunit
- Protein Kinase activity
2) Regulatory (R) Subunit
- each binding site contains 2 binding sites for cAMP

Stimulates glycogen breakdown
Inhibits glycogen synthesis by phosphorylating glycogen synthase

24
Q

Phosphorylase Kinase

A

Kinase that activates glycogen phosphorylase by phosphorylation of serine which converts it from b form to A form

Has several forms: subunit composition ABYDx4

  • Y subunit-catalytic subunit
  • ABD regulatory subunit
    1) D subunit (calmodulin)-binds Ca2+
  • serves as Ca2+ sensor
  • activates many pathways
  • contains 4 calcium binding sites
    2) B subunit is target for phosphorylation

Duel Control:

1) Phosphorylation ser activated by protein kinase A
2) Calcium-which is released from sarcoplasmic reticulum due to nerve impulse to stimulate muscle contraction

25
Q

Lysosomal Degradation of Glycogen

A

alpha (1-4) glucosidase (aka acid maltase)

-degrades glycogen from vacuoles in cytoplasm

26
Q

Glycogen Synthesis Overview reaction

A

1) alpha-D-glucose-> Glucose 6-Phosphate catalyzed by Hexokinase at the expense of ATP-> ADP
2) Glucose 6-Phosphate-> Glucose 1-Phosphate catalyzed by phosphoglucomutase
3) Glucose 1-Phosphate-> UDP Glucose catalyzed by UDP Glucose pyrophosphorylase at expense of UTP
4) UDP-Glucose-> Glycogen catalyzed by Glycogen Synthase

27
Q

Hexokinase

A

Glycolytic Enzyme

Converts:
Alpha-D-Glucose-> Glucose 6-Phosphate at expense of ATP

28
Q

Phosphoglucomutase

A

Interconverts Glucose 1-Phosphate and Glucose 6-Phosphate

29
Q

UDP-glucose pyrophosphorylase

A

Converts
Glucose 1-Phosphate + Uridine Triphosphate (UTP)-> UDP-Glucose + Pyrophosphate (PPi)

Pyrophosphate is hydrolyzed to 2Pi (orthophosphates) to provide energy

30
Q

Inorganic Pyrophosphatase (Pi)

A

Hydrolyzes PPi-> Pi + Pi

-exergonic-> drives glycogen synthesis

31
Q

Glycogen Synthase

A

UDP-Glucose + existing Glycogen molecule-> UDP + Glycogen (n+1)

adds glucose to glycogen

  • requires existing polymer of glycogen with at least 4 glucose residues
  • glycogenin
32
Q

Nucleotide diphosphate Kinase

A

Regenerates UTP

UDP + ATP-> UTP + ADP

33
Q

Glycogenin

A

Serves as a primer for glycogen synthesis

  • contains tyrosine residue-OH
  • location where glycogen molecules have glucose released/attached
34
Q

Branching Enzyme

A

synthesizes alpha 1-6 branches every 8-10 glucose residues during glycogen anabolism

35
Q

Insulin

A

Peptide Hormone

  • secreted by islets of Langerhans in pancreas
  • released in response to high blood glucose concentration (Well fed state)
  • Stimulates anabolism of glycogen in liver (NOT MUSCLE) by binding to insulin receptor
36
Q

Protein Phosphatase 1

A

Dephosphorylates Ser and Thr

  • Dephosphorylates glycogen synthase b (inactive form) converting it into glycogen synthase a (active form) which stimulates glycogen synthesis
  • Dephosphorylates phosphorylase kinase inhibiting glycogen breakdown

MC Biochem 2 (31 decks)

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