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BIOL304 > Chapter 21 (Glycogen Synthesis and Degradation) > Flashcards

Chapter 21 (Glycogen Synthesis and Degradation) Flashcards

1
Q

Where does Glycogen metabolism Occur

A
  1. Liver
  2. Skeletal Muscles
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2
Q

Overall enzyme deficiencies in glycogen metabolism

A

Leads to problems in Liver + muscles = they don’t function normally
- Can create issue in diaphragm = THEN have large problem –> get lung problem – lungs get infected = can die from infection

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3
Q

What type of muscle is the diaphragm

A

Skeletal muscle – if have issue in glycogen metabolism = then can have issue in diaphragm because its a skeletal muscle that relies on glycogen metabolism –> issue in diaphragm can cause lung infection = can die

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4
Q

Structure of Glycogen

A

Glycogen is a highly branched homopolymer of glucose
- Has Alpha 1,4 and Alpha 1,6 bonds
- Has a reducing and a non-reducing end (non-reducing ands have free OH group)

***Glycogen molecuke has 12 layers of flucose molecules – can have 55,000 glucose residues
- Most of the glucose is linked by 1,4 bonds BUT it is branched every 12 residues by 1,6 bonds
- Alpha glycolidic links can form helical polymers

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5
Q

Where is glycogen found

A

Found in the cytoplasm of all tissues

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6
Q

Middle of the Adrenal gland

A

Medula

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7
Q

What does the Medula release

A

Catacolin – Catacolin = epinerphrine + Norepinephrine

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8
Q

Where are the largest stores of Glycogen

A

Liver + Skeletal mucles

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9
Q

Liver + glycogen

A

Liver breaks down glycogen and releases glucose into the blood to provide energy for the brain and Red Blood Cells

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10
Q

Skeletal Muscle + Glycogen

A

Skeletal Muscle glycogen stored are used to provide energy for muscle contraction

***ATP helps Myosin + Actin connect = contract muscle

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11
Q

Glycogen degradation steps

A
  1. Release of Glu-1-P from glycogen
  2. Remodeling of Glycogen to allow for continued degradations
  3. Conversion of Glu-1-P into Glu-6-P
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12
Q

Fates of Glu-6-P

A
  1. Processing by the Glycolytic pathway
  2. Conversion into free free glucose for release into the blood
    - Mainly occurs in the liver
  3. Precessing by the Pentose Phosphate pathway (Produces NADPH)
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13
Q

Glycogen metabolism is…

A

The regulated release and storage of Glucose

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14
Q

What is required for Glycogen synthesis

A

requires an activated form of glucose – UDP-Glucose

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15
Q

What is an activated form of Glucose

A

UDP-Glucose

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16
Q

How is UDP-Glucose formed

A

Formed by the reaction of UTP and Glu-1-P

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17
Q

Regulation of Glycogen degradation and synthesis

A

Glycogen degradation and synthesis are reciprocally regulated

***Regulation of glycogen degradation is complex

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18
Q

Issue with glucose

A

Glucose is an important furl BUT glucose can’t be stored because high concetaryions of glucose would disprut the osmotic balance –> would cause cell damage or death

Solution: Store glucose as non-osmotocally active glycogen

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19
Q

Glycogen

A

readily mobilized storage form of glucose

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20
Q

Use of glycogen

A

Can be broken down to yield glucose when energy is needed

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21
Q

Glycogen vs. FA

A

Glycogen = not as reduced as Fatty Acids = not as energy rich

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22
Q

Why isn’t all excess fuel stored as FA rather than glycogen

A

Controlled release of glucose from glycogen = maintains blood-glucose concentration between means –> circulating blood keeps the brain supplied with glucose –> glucose is used by the brain as fuel
- Readily mobilized glucose from glycogen = good source of energy for sudden activity
+ Unlike fatty acids – the release pf glucose can occur without Oxygen = can supply energy in aerobic environment
***Couldn’t have the same effect with FA

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23
Q

What organisms have Glycogen

A

Archea + Bacteria + Euk
**Plants = store glucose as starch
**Storing glucose as a homopolymer is common in all life forms

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24
Q

Amount of glycogen in Muscles vs. liver

A

Higher concentration of Glycogen in muscles BUT there is more glycogen stored in skeletal muscles overall because muscles make up more mass

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25
Q

Use of Glycogen Synthesis and degradation

A

Liver –> Glycogen synthesis + degradation is used to maintain blood-glucose levels

Muscle –> Glycogen synthesis and degradation is used to regulate energy need in muscle itself

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26
Q

When does glycogen synthesis occur

A

Occurs when glucose is abundant

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27
Q

Why is glycogen regulation complex

A

Partly because all of the enzymes involved in glycogen metabolism + its regulation are associated with glycogen particle

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28
Q

Glycogen metabolism (overall)

A
  1. Several enzymes in glycogen metabolsim = allostarically respond to metabolites that singla energy needs of the cell
  2. Hormones can intiate signal cascade that leads to reversible phosphorylation = alters catalytic sites
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29
Q

Hormone reductions + glycogen metabolism

A

Reduction of hormones adjust glycogen metabolism to meet the needs of the organism

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30
Q

Glycogen Phosphorylase

A

Degrades glycogen from the non-reducing end

 - Phosphorylase catalyzes a phsphorylsis reactions that yields glucose-1-P  ***Creates Glucose-1-P

Reactions: Glycogen (n) + Pi –> Glu-6-P + Glycogen (n-1)

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31
Q

Phosphoglucomutase

A

Converts Glucose-1-P to Glucose-6-P
***Does not use ATP

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32
Q

Requirements for Glycogen Phosphorylase

A

Requires Pryidoxal Phosphate (PLP) cofactor

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33
Q

Use of PLP

A

Required for Glycogen Phosphorylase

Use – forms Schiff base with a Lysin residue at the active site of phosphorylase
***Requires Lysine

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34
Q

Glycogen –> Glu-6-P enzymes activties

A

Requires 4 enzyme activities

  1. 1 enszymes to Degrade glycogen
  2. 2 enzymes to Remodel Glycoegn
  3. 1 enzyme fo convert the product of glycogen breakdown into a form sutable for metabalism
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35
Q

Hey enzyme in glycogen vreakdown

A

Glycogen Phosphorylase

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36
Q

How does Glycogen Phosphorylase work

A

Cleaves substate by adding Pi –> yeilds Glu-1-P

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37
Q

Phosphoprylysis

A

Cleavage of a bond by adding Pi
***done by glycogen phsophorylase

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38
Q

Glycogen phosphorylase (Textbook)

A

Catylzyes the sequental removal of glycosyl group of the non-reducing end of glycogen molecule

**Pi splits the glycosidic link betwen C1 of the terminal residue and C4 of the adjacent one
**retains the alpha configuration
***Cleaves bond between C1 and glycosidic Oxygen

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39
Q

Reversibility of the phosphorylase reaction

A

Phosphorylase reactions is readily reversible

pH = 6.8 –> ratio of Pi to glucose is 3.6

dG = very small because of the glycosidic link is replaced by a phosphoryl etser nond that has equal transfer potential

BUT phosphorylysios prcoeeded in foward directions of glycogen breakdown because the Pi/Glu-6-P ration is >100 = favors phosphorylysis

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40
Q

Why does phosphoylysis go fowards

A

Phosphorylysis proceeded in forward directions of glycogen breakdown because the Pi/Glu-6-P ration is >100 = favors phosphorylysis
***Shows cells ability to alter delta G to favor reaction occurance by altering ratio

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41
Q

Energy of Phosphpylysis

A

Phophorylitic cleavage of glycogen = energetically favoarbey becayuse released sugar is already phosphorylated

VS.
if it used hydrolytic activity –> then it would yeild a glucose –> the glucose would then have the be phosphorylated at the expense of ATP

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42
Q

Issue if Phosphorylase

A

Cleaving the glycogen with phosphate rather than hydrolitically means that water needs to be excluded from the active site

43
Q

Structure of phosphorylase

A

Dimer with idetical subunits
- each Sub unit os completley folded into amino terminal domain containing a glycogen binding site and an carboxy terminal domain

- the catalytic site in each sub unit = located in the deep crevice formed by residues from both domains 
- Substrates bind at the same time = causes the creavice to narrow

***Structure is done this way in order to exclude water

44
Q

Clues that suggest mechanism of phosphorylase

A

1 – both glycogen and Glu-1-P have alpha at C1 –> IF there was a direct attack of Phophate at C1 then there would be inversion of configuaration at the carbon because the reaction woudl proceed via penta covalent intermediate
BUT we know that Glu-1-P formed has alpha configuration = suggests that there is an EVEN number of steps
- LEADS to likley explination that there us a carbocation intermediate

2 – Mechanism requires a coenzyme PLP – the aldehyde on the coenzyme = forms a schiff base link with Lysine in enzyme
- Studies show that the Pi takes the position between the 5’ phosphate of PLP and glycogen substrate
- Pi donates H+ to oxygen on C4 of glycogen + at the same time aquires a H+ from PLP
- carbocation intermediate = attacked by Pi = get Glu-1-P + return PLP

45
Q

PLP vitamin

A

PLP is a derivative of B6

46
Q

Glycogen binding site in Phosphorylase

A

Glycogen binidng site is 30A away form the catalytic site BUT it is connected to the catalytic site by a narrow crevice that can fit 4-5 glucose units

47
Q

Seperaration between catalytic site and binding site in Phosphorylase

A

Enables the enzyme to phosphorylate many resides without having to dissociate and reassociate after catalytic cycle

48
Q

Processive enzyme

A

Enzyme that is able to catyluze many reactions without having to dissciate and reassociate after each catalytic cycle

Example – phosphorylase
***Property of enzymes that synthesize and degrade large polymers

49
Q

Use of PLP in phosphorylase

A

The phosphate substrate promotes the cleavage of a alpha 1,4 bond in glycogen by donating a proton to the departing glucose –> results in a carbocation intermediate

50
Q

Intermediate in phosphorylase mechanism

A

Carbocation intermediate – carbocation intermediate and phosphate combine to form Glu-1-P

51
Q

1,4 bonds vs. 1,6 bonds

A

1,4 bonds = don’t break easily
1,6 bonds = break easier

52
Q

Amino Acids in Glycogen Phosphorylase

A
  1. Lys 680
  2. Gly135
  3. Gly134
  4. Arg 569
  5. Lys 568

***Also uses a PLP

53
Q

Schiff base Alternative name

A

Schiff base = Iminie

54
Q

Schiff base formation

A

Schiff base is formed by the reaction of a primary amine with an aldehyde or a Ketone

PLP- forms a schiff base with lysine in phosphorylase active site

55
Q

Phosphorylase Mechenism (Image)

A
56
Q

Second enzyme needed for glycogen breakdown

A

A debranching enzyme

57
Q

Limitation of Phosphorylase

A

Phosphorylase acting alone = degrades glycogen to a limited extent –> it can break 1,4 bonds BUT it can’t cleave 1,6 Bonds

***Alpha 1,6 bonds are not sucetable to Phosphorylase
- phosphorylase stops cleaving 1,4 links when it reaches terminal residue 4 residues away from branch point
- Because 1 in 12 residues = bracnching residue – clevage by only phosphorylase alone would come to a later after 8 glucse residues per branch

58
Q

How is the remainder of glycogen molecule mobilized for use as fuel

A

After phosphorylase – have transferase + Alpha 1,6 glucosides

59
Q

Transferase + Alpha 1,6 glucosides

A

remodel glycoegn – allows form continued degradation by phosphorylase

***Can remodel –> then phosphorylase can keep working

60
Q

Transferase

A

Shifts a block of 3 glycogen residues from outter branch to another

- Transferase exposes a single glusode resiude joined by Alpha 1,6 bonds
 - Transferase = shifts a small oligiosaccaride near a branch point to a neaby chain --> therebu making the glucose moeities accesible to phosphorlase
61
Q

Glycogen remodeling

A
  1. Transferase – Shifts a block of 3 glycogen residues from outter branch to another –> Transferase exposes a single glusode resiude joined by Alpha 1,6 bonds
  2. Alpha glucosidease = hydrozlyses the 1,6 bond

THEN phosphorylase can keep working

Overall – 1,6 Glucosidase + transferase convert branched structured into linear –> paves the way for further clevage by Phosphorylase

62
Q

Alpha 1,6 glucosidease

A

Debranching enzyme – hydrolyzses 1,6 bonds

  - Clevase the 1,6 bonds at the branching point = releases a free glucose  
  - Uses a Water

***The free glucose is relases and can be phosphorylated by hexokinase to go to glycolysis or to PPP

63
Q

Transferase and 1,6 glucosidase in Euk

A

In Euk – they are present in one polypeptide chain = they are a bifunctional enzyme

64
Q

Glycogen remodeling (image)

A
65
Q

Phosphoglucomutase

A

Converts Glu-1-P to Glucose-6-P

***Causes shift in phosphate group

66
Q

Active site of Phosphoglucomutase

A

Conatains a Phosphorylated Serine in the active site

67
Q

Intemediate of Phosphoglucomutase

A

Phosphoglucomutase forms a Glucose 1,6 bisphosphate intermediate
- Forms the intermediate by donating its bound phosphoryl group to Glucose-1-P
- The phosphoryl group is restored to the enzyme with the formations of Glu-6-P

68
Q

Phosphoglucomutase reactions (image)

A
69
Q

Next steps after Glu-1-P is formed

A

Onces Glu-1-P is formed –> needs to be converted to Glu-6-P to enter the metabolic mainstream

70
Q

Phosphoglumutase reaction (depth)

A

The enzyme adds phostphate to Glu-1-P at the cataklytic site (done so because have a phophate on Serine resiude at the catalytic site) – the phosphorylk group is transfered from Serine to the C6 OH of Glu-1-P = forms Glu-1,6-BP

THEN C1 phosphate group = shyttled to the serine reidude –> donates the phosate at C1 to the Serine residue –> form Glu-6-P + regernates the phosphorylated enzyme

71
Q

What is found in the liver that is absent in the Muscle

A

Liver contains a hydrolytoc enzyme Glu-6-Phaphatse that is not found in the muscle

72
Q

Glu-6-Phosphatse

A

Glu-6-P –> Glucose

***Found in teh liver

Reaction – Glu-6-P + water –> Glucose + pi

**Free glucose is relased into the blood for use by other tissues such at the brain and RBCs
**Same enzyme that relases free glucose at the end of glucogenssis
***Located in the lumen side of the SER membrane – Glu-6-P goes to the ER –> Glu + Pi –> Leave cell

73
Q

Glu-6-Phosphatse throughout the body

A

Glu-6-Phosphatse = absent from most other tissues

74
Q

Glu-6-P in mucles

A

Muscle tissues retain their Glu-6-P for ATP syntehsis
***NO ATP = the muscle won’t contract

75
Q

What is needed for muscle contraction

A

ATP + Ca2+

76
Q

Glucose in muscle vs. liver

A

Muscle –> Glucose-6-P = used to generate ATP

Vs.

Liver –> Glucose is not the major fuel for the liver

77
Q

Fuel for the brain

A

Glucose

78
Q

What if you have an issue in smooth muscles

A

Bad for blood flow

79
Q

Major function of the Liver

A

To maintain a nearly constant concentration of glucose in the blood

***Role = to form glucose to exprot to other tissues when blood glucose concentration is low

Liver = releases glucose into the blood between meals + during musclular activity

80
Q

Released glucose from liver

A

Taken up porimarly by the brain + skelatal muscles + RBCs

81
Q

Phosphorlated glucose made from glycogen degradation in liver

A

NOT trasnprted out of the cell –> liver needs to convert it to Glucose to be able to release it = has Glu-6-Phosphatse to be able to do so

82
Q

How is phosphorylase regulated

A
  1. Allosteric Interactions – signla energy state of cell
  2. Reversible interactions – responsive to hgromones (Insulin + epinepherine + Glucogon)
83
Q

Key regulatory enzyme in Glycogen degradation

A

Glycogen Phosphorylase
***Glycogen degradation = orecicley contrilled by multpple interlocking mechanisms BUT the focus of control - Glycogen phosphpylase

84
Q

Forms of Glycogen phosphorylase

A
  1. B form –> LESS active
  2. A form –> MORE active
85
Q

A form vs. B form

A

A from = has a phosphorylated Serine residue
***Makes it MORE active

A form = exhibits most responsible R –> T transition

86
Q

Equillibruim of A form and B from

A

Both in equillibrium between R and T states

BUT

B form –> T starte is favored (Tense = Less active)
A form –> R state is favored (Relaxed = active)

87
Q

Liver regulation vs. Muscle regulation

A

They are regulated differentley because liver maintains glucose homeostasis of the organism but the muscle uses glucose for energy for itself

88
Q

Key role of liver

A

To maintain adequate blood glucose levels

89
Q

Default state of liver Phosphorylase

A

a from –> R state
***Liver phosphorylase is prepared to generate blood glucose unless signalled otherwise (because its always in the active A form)

90
Q

Glucose as a regulator for Liver phosphorylase

A

Glucose is a negative regulator for liver phosphorylase –> facilitates the transition from R state to T state (Active –> Inactive)

Have Glucose = in the T state (glucose puts it in the T state = inactive)

**Enzyme reverts to T state only if it senses the presence of sufficient glucose
**If glucose is present in diet then there is no need to degrade glycogen

91
Q

Liver phosphorylase vs. Muscle phosphorylase

A

Isozymes

92
Q

How is Muscle phosphorylase regulated

A

Regulated by Intracellular energy charge

93
Q

Default form of Phosphorylase in Muscle

A

b form –> in the T state
***Because the phosphorylase must be active during muscle contraction

94
Q

Regulation of Muscle phosphorylase

A

When energy is needed (Increase in AMP) –> Phosphorylase binds to AMP = stabilizes the phosphorylase in the R state = active = degrades glycogen
- B form is Activated by increase in AMP –> AMP binds to the nucleotide binding site = stabilized teh confirmation of B in the R state = active – means that when a muscle contracts and ATP decrease –> AMP binds –> phosphorylase is signalled to degarde glycogen (uses Mysin + Adenylate Kinase)

VS.

T state = stabilized by ATP and glu-6-P = won’t degrdae glycogen
- When ATP is unavalble – Glu-6-P may bind to the ATP binding spot = stabilizes in the less actove form = feedback inhibition
- In resting states B = inactive bevause of inhibtor affects of ATP and Glu-6-P BUT a form is fully active regardless of concentration of AMP,ATP, and Glu-6-P

95
Q

Liver Glu-6-P + AMP

A

Glucose-6-Phosphatse = insenstive to regulation by AMP because liver does not undergo dramatic chnages in Energy charge

96
Q

What does the differnce in regulation of liver vs. muscle isozyme show?

A

Shows exmaple of the use of isozymes to establish tissue specific biochemical properties of liver + muscle

***Isozymes = 90% idetical in AA sequence yet 10% difference is subyle but improitant shift in regualtion

97
Q

Three types of skeletal muscles

A
  1. Type 1 –> Slow twitch
  2. Type 2b –> Fast twitch fibers
  3. Type 2a –> Intermediate between types
98
Q

Type 1

A

Slow twitch fibers –> use cell respiration powered by FA degradation to generate ATP
***Glycogen is not an important energy source for these fibers – has lower amounts of glycogen phosphotase
- relies of CR
- Powered by FA degradation
- Rich in mitocondria
- powers endurace

FA = good energy storage form BUT generating ATP from Fatty acids is slower

99
Q

Type 2b

A

Fast-twitch fibers – generate energy by aeorobic glycosis + prefrom little Cell respiration
***Mitocondria are rare and glycogen is the primary fuel for them
- Glycogen = main fuel –> have more glycogen Phosphorylase
- Fibers are rich inglycolitic ensymes –> needed to process glucose quickly in absense of Oxygen
- Poor in mitocndira
- Powers burst activities

100
Q

Type 2a fibers

A

Process properties intermediate between the two fibers

101
Q

Converting between muscle types

A

No amount of training can interconvert type 1 and Type 2b BUT type 2a is trainable

102
Q

FA as a fuel

A

FA = good energy storage form BUT generating ATP from Fatty acids is slower

103
Q

Biochemical properties of muscle fiber types

A

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