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Biochem 311 > Lecture 3 - Glycogen Metabolism > Flashcards

Lecture 3 - Glycogen Metabolism Flashcards

Glycogen Metabolism and Regulation of Metabolic Pathways

1
Q

What is the most abundance polysaccharide?

A

cellulose; about 10^12 tons of it are synthesized each year; mostly from plants; structural polysaccharide from glucose

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2
Q

what are the 4 functions of polysaccharides?

A

structural, food storage, cell surfaces, and extracellular matrices

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3
Q

Where are starch and glycogen found?

A

Starch = plant cells
Glycogen = animal cells
Forms of energy storage that can be broken down for ATP

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4
Q

How are polysaccharides important to cell surfaces and extracellular matrices?

A
  • Many kinds of proteins and lipids have polysaccharides components attached to them - usually on cell surfaces
  • ECM is a major physical barrier
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5
Q

What is a disaccharide?

A

two sugars that are joined together via glycosidic bond

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6
Q

How is sucrose formed?

A

1,2 linked alpha glucose and beta fructose
- alpha - 1,2 - glycosidic linkage

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7
Q

What are sources of sucrose?

A

sugar cane, sugar beet

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8
Q

How is lactose formed?

A

1,4 linked beta-galactose and alpha-glucose
- beta-1,4-glycosidic linkage

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9
Q

What is a source for lactose?

A

milk

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10
Q

How is maltose formed?

A

1,4 linked alpha-glucose and another alpha-glucose
- alpha-1,4-glycosidic linkage

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11
Q

What is the source of maltose?

A

hydrolyzed starch aka formed thru partial degradation of starches

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12
Q

What might be the most diverse biomolecule in nature?

A

polysaccharides

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13
Q

What can you make from one 6 carbon hexopyranose sugar vs from one amino acid or nucleotide?

A
  • the sugar such as glucose can make 11 diff disaccharides and 8 of those lead to infinite polymers; bc of having so many diff chiral centers
  • you can make only a single two nucleotide change or a two amino acid polypeptide; more restriction in isomeric forms
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14
Q

How many glucose molecules are in cellulose?

A

about 5,000-10,000

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15
Q

What glycosidic linkage is present within cellulose molecules?

A

beta-1,4-glycosidic linkage

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16
Q

What is cellulose found in?

A

some bacteria, algae, fungi, seed hairs, and animals (tunicates or sea squirts)

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17
Q

What are wood cell fiber cells walls made of? (3 things)

A

cellulose, lignin, and hemicelluloses

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18
Q

Why can’t humans digest cellulose?

A

humans do not have the enzymes that can break the beta-1,4-glycosidic bonds present within cellulose; certain bacteria, fungi, protozoa do

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19
Q

Can humans break down starch?

A

yes, starches provide the bulk of energy we obtain from grains, potatoes, etc

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20
Q

How many different types of glucose polymers are present in starch?

A

two kinds of D-glucose polymers found as an energy storage material in foods

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21
Q

What are the two kinds of D-glucose polymers?

A

amylose and amylopectin

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22
Q

What is amylose?

A

long unbranched chains of D-glucose that are linked thru alpha 1,4 linkages

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23
Q

What is amylopectin?

A

more branching, alpha 1,4 linked glucose with alpha 1,6 linkages at branch points; branching is mediated by which carbons are connecting for glycosidic linkage

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24
Q

What induces the branch point seen in glycogen?

A

alpha 1,6 linkages; all has to do with the position of glucose units

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25
Q

What are major sites of glycogen storage?

A

liver and muscle; mammals usually store in liver but can also store in muscle

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26
Q

Why is glucose not stored in monomeric form?

A

polymers of glucose (aka glycogen) are insoluble so they contribute little to cellular osmolarity whereas soluble glucose greatly affects osmotic cellular conditions that (favors water influx aka cell bursting)

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27
Q

Why is glycogenin important?

A

it is important for the synthesis of the primer (short piece of glucose polymers) which you can build the particle off of

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28
Q

What two reactions does glycogenin catalyze?

A
  • will involve transfer UDP-glucose to glycogenin protein
  • transfer of glucosyl residues to existing glucose(n)-glycogenin
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29
Q

What does glycogenin form?

A

glycogen molecule primer of 8 glucosyl residues that are linked via alpha 1,4 glycosidic bonds

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30
Q

What is the glycogen particle structure like?

A
  • glycogenin glucose chain in center
  • glycogen chains of 12-14 residues exist in tiers
  • inner chains have 2 alpha 1,6 branches each
  • unbranched outer tiers
  • 12 ties in mature particle (about 55k glucose residues, about 21 mm diameter
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31
Q

What are two examples of catabolic pathways?

A

glycogenolysis and glycolysis

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32
Q

What is glycogenolysis?

A

Glycogen to Glu-6-P

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33
Q

What is glycolysis?

A

Glu-6-P to Pyruvate

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34
Q

What are two examples of anabolic pathways?

A

Gluconeogenesis and glycogenesis

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35
Q

What is gluconeogenesis?

A

Pyruvate to Glu

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36
Q

What is glycogenesis?

A

Glu to Glycogen

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37
Q

What does glycogen phosphorylase do?

A
  1. Removes glucose units from glycogen one at a time
  2. Transfers phosphate group to the glucose units it removes
  • Glycogen + inorganic phosphate to glycogen + Glucose 1- Phosphate
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38
Q

What does Phosphoglucomutase do?

A
  1. Takes substrate and isomerizes it
    - Glucose 1-phosphate to Glucose 6-phosphate
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39
Q

What does Glucose-6-phosphatase do?

A
  • In the liver: phosphate group is removed to form glucose and inorganic phosphate (Glucose 6-phosphate + H20 to Glucose and inorganic phosphate)
  • Muscles do not have this enzyme
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40
Q

What does liver glycogen serve as?

A

energy reservoir for entire body; glucose in the brain or other tissues will be glucose from diet or glucose that is released from glycogen stores in liver

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41
Q

How many enzyme activities are required for the removal of branch points?

A

Two: tandem enzyme has two activities present in same polypeptide (done in sequence)

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42
Q

How are branch points removed?

A
  1. debranching enzyme removes 3 of 4 terminal glucosyl residues and transfers to the straight chain
  2. alpha 1,6 glucosidase (same enzyme just diff role) removes the 4th residue as free glucose (removes alpha 1,6 branch points)
43
Q

What is a tandem enzyme?

A

two activities present on a single protein molecule

44
Q

On what end does glycogen phosphorylase act on?

A

nonreducing end; C1 is apart of glycosidic bond

45
Q

What are nonreducing sugars?

A

sugars that reduce mild oxidizing agents (ex: ferric Fe 2+ or cupric Cu2+); aldehyde is oxidized to form a carboxyl group

46
Q

What did the Fehling’s rxn test for?

A

tested for glucose using glucose oxidase (currently used, more sensitive); tested glucose in urine to see if someone was diabetic; would reduce copper ions leading to a detectable color change

47
Q

How many tests are used to determine glucose in diabetics?

A

two

48
Q

Can phosphorylase act on branched chains?

A

No only straight changes so debranching enzyme must first take care of branch points

49
Q

How exactly does phosphoglucomutase work? 3 steps.

A
  1. Serine within phosphoglucomutase will undergo phosphorylation (needed to isomerize glucose)
  2. Phosphate group from serine goes to glucose 1-phosphate substrate = now have glucose 1,6 bisphosphate
  3. Phosphate at C1 position will go to serine (regenerating enzyme) and making Glucose 6-Phosphate
50
Q

What feeds into glycolysis?

A

glucose 6-phosphate

51
Q

Where is glucose 6-phosphatase located?

A

embedded in the ER membrane

52
Q

What are the steps to glucose 6-phosphatase activity?

A
  1. G6P is transported from the cytosol to the ER lumen
  2. Glucose 6-phosphatase dephosphorylates G6P
  3. Glucose leaves ER lumen
  4. Glut 2 transfers glucose into the blood stream
    - liver has this particular enzyme
53
Q

What does UDPG stand for?

A

uridine diphosphate glucose

54
Q

What is UDPG?

A

an active donor of glucosyl units in growing polysaccharide chains

55
Q

What needs to happen for glucose to be added to glycogen?

A

glucose has to be activated by UDP (this biochemically targets it for glycogen incorporation); UTP has 3rd phosphate group removed and then UDP is attached to glucose

56
Q

What does glycogen synthase do?

A

makes alpha 1-4 glycosidic bonds

57
Q

What does the branching enzyme do?

A

transplants a short chain to introduce a branch by forming an alpha 1-6 glycosidic bond

58
Q

What does hexokinase do?

A

Glucose + ATP makes Glucose 6-phosphate and ADP; glycogen breakdown isn’t only way to make G6P

59
Q

What does phosphoglucomutase do during glycogen synthesis?

A
  • a reversible rxn (can favor either forward or reverse rxn)
  • Glucose 6-phospate to glucose 1-phosphate
60
Q

What does UDP-glucose pyrophosphorylase do?

A

UTP + Glucose 1-phosphate leads to UDP-Glucose + pyrophosphate

61
Q

What does pyrophosphatase do?

A

pyrophosphate + H2O to 2 inorganic phosphate + H+
- generating free energy in this step

62
Q

What are the 6 steps in glycogen synthesis?

A
  1. Glucose to G6P
  2. G6P to Glucose 1-phosphate
  3. Glucose 1-phosphate to UDP-glucose
  4. UDP-glucose added to glycogen chain
  5. Pyrophosphate to 2 molecules of inorganic phosphate
  6. role of branching enzyme
63
Q

What is insulin?

A

a hormone that lowers blood glucose levels

64
Q

How does insulin lower blood glucose levels?

A
  • inhibits glycogen breakdown (promotes glycogen synthesis)
  • inhibits gluconeogenesis
65
Q

How does gluconeogenesis work?

A

making glucose from noncarbohydrate precursors
- lactate and pyruvate can provide carbon skeletons that are needed for glucose synthesis

66
Q

How is the glycogen synthesis process stimulated?

A

by stimulation of uptake of glucose into liver and muscle cells

67
Q

What do epinephrine and glucagon do?

A

raise blood glucose levels by stimulating glycogen breakdown and by stimulating gluconeogenesis

68
Q

What is epinephrine important for?

A

fight or flight response; when you have this response you need energy so the need for glucose increases (glucose which can be provided via glycogen breakdown)

69
Q

What does glucagon deal with?

A

short term starvation; stimulates glycogen breakdown in the liver so that glucose is available to the brain and other tissues (epi can do but mainly done by glucagon)

70
Q

Where do glucagon and epi respectively work?

A

glucagon = liver
epi = liver and muscle

71
Q

Compare and contrast fates of glycogen in liver and muscle

A
  • both have increase in glycogenolysis
  • decreased glycolysis in liver, increased in muscles
  • increased gluconeogenesis in liver only
72
Q

When you have high blood glucose, how is glycolysis increased in the liver?

A
  • Glut2 leads to increased glucose concentration inside the cell which leads to increase in glycolysis
  • an increase in insulin leads to synthesis of hexokinase II, PFK1, pyruvate kinase
73
Q

What is the effect of increased glycolysis when you have high blood glucose?

A

ATP creation is needed when to promote glycogen synthesis

74
Q

What does insulin do when you have high blood glucose?

A
  • increases insulin sensitive protein kinase activity
  • increases PKB activity
  • makes hexokinase II, PFK-1, and pyruvate kinase
75
Q

How is there an increase in glycogen synthesis when you have high blood glucose? (4 steps)

A
  1. Insulin binds to receptor
  2. Enzyme PKB (kinase) is stimulated and its activity increases
  3. Inhibition of GSK-3 activity (kinase and substrate for PKB)
  4. Low levels of GSK-3 will favor activation and increase in activity of glycogen synthase
  5. Glycogen synthesis increases!
76
Q

What would active GSK-3 do?

A

inhibit glycogen synthase

77
Q

How does glycogen breakdown reduction occur when you have high blood glucose? (5 steps)

A
  1. Insulin stimulates increase in Insulin-sensitive protein kinase
  2. Increase in PP1 activity (a phosphatase)
  3. GSK inhibition and PP1 activation will dephosphorylate any residues on glycogen synthase (combined effects will activate glycogen synthase)
  4. PP1 dephosphorylates glycogen phosphorylase and phosphorylase kinase
  5. Glycogen breakdown is reduced as activities of both proteins are decreased
78
Q

When active, what does phosphorylase kinase do?

A

increases glycogen phosphorylase

79
Q

What 3 things happen when you have low blood glucose?

A
  • increase in glycogen breakdown
  • decrease in glycogen synthesis
  • decrease in glycolysis
80
Q

How is glycogen synthesis decreased when you have low blood glucose? 5 steps

A
  1. Increase in glucagon
  2. Glucagon activates cAMP
  3. cAMP activates the kinase PKA (phosphorylates a bunch of different things)
  4. PKA will phosphorylate glycogen synthase and thus inhibit it
  5. Decrease in glycogen synthesis
81
Q

How is glycogen breakdown increased when you have low blood glucose? 6 steps

A
  1. Increase in glucagon
  2. Glucagon activates cAMP
  3. cAMP activates the kinase PKA (phosphorylates a bunch of different things)
  4. PKA phosphorylates Phosphorylase Kinase
  5. Active Phosphorylase kinase will activate Glycogen Phosphorylase
  6. Increase in glycogen breakdown
82
Q

How does hormonal control of glycogen breakdown work?

A
  1. Hormone activates adenyl cyclase
  2. Adenyl cyclase activates ATP into cAMP
  3. cAMP activates PKA
  4. cAMP activates phosphorylase kinase, ATP to ADP conversion step here
  5. Phosphorylase kinase activates glycogen phosphorylase, 2 ATP to 2 ADP
83
Q

How is adenyl cyclase activated?

A

thru the g-protein system

84
Q

Is insulin a g protein coupled receptor?

A

no

85
Q

What is an example of an allosteric regulator?

A

cAMP; ATP makes cAMP and pyrophosphate catalyzed adenyl cyclase

86
Q

What factors influence enzyme activity?

A
  • phosphorylation
  • allosteric regulation
  • covalent modification
  • transcriptional control
87
Q

What are 2 allosteric effectors of glycogen phosphorylase & what do they do?

A
  • ATP, glucose 6-phosphate (inhibits phosphorylase)
  • AMP (activates phosphorylase)
88
Q

What happens when cell is in a high energy state?

A

won’t need further breakdown of glycogen

89
Q

What happens when you have a high concentration of AMP?

A

lots of ATP is used so you need more and need glycogen breakdown

90
Q

How does covalent modification of glycogen phosphorylase occur?

A
  • serine residue on phosphorylase (tetramer) can be phosphorylated (prefers increased activity) or dephosphorylated (lower activity)
  • covalent modif is under hormonal control
91
Q

What is the shape of the active form of glycogen phosphorylase?

A

dimer

92
Q

What type of mechanisms regulate glycogen phosphorylase activity?

A

both covalent and noncovalent control; latter is thru allosteric effect control

93
Q

What do T and R states refer to?

A

T = inactive form of an enzyme
R - more active state of enzyme
used in reference to glycogen phosphorylase here

94
Q

How does hormonal control of glycogen synthesis occur?

A
  • Glycogen synthase is covalently modified by phosphorylating serine by PKA
  • Phosphorylated glycogen synthase = inactive
  • Phosphorylated form of phosphorylase = active
95
Q

How do you know which site of GM (glycogen targeting) protein will be active?

A

depending on which mode is operational (breakdown or synthesis); phosphorylated site ctrls what happens

96
Q

What site does insulin phosphorylate?

A

GM site 1

97
Q

What happens when Insulin phosphorylates GM site 1?

A
  1. Activation of PP1
  2. Dephosphorylation of glycogen phosphorylase kinase, glycogen phosphorylase, and glycogen synthase
98
Q

What site does epinephrine phosphorylate? (also glucagon)

A

GM site 2

99
Q

What does epinephrine phosphorylation of GM site 2 cause?

A
  1. PP1 disassociates from glycogen particle
  2. PP1 can’t access glycogen phosphorylase and glycogen synthase
  3. PKA phosphorylates inhibitor of PP!
100
Q

Net goal of insulin?

A

inhibit glycogen breakdown/stimulates its synthesis

101
Q

Net goal of epi (and glucagon in liver)?

A

activate glycogen breakdown/inhibit its synthesis

102
Q

What else does GM do?

A

recruits other players impt for glycogen metabolism

103
Q

How does insulin inhibit GSK3 activity?

A
  • inhibits thru various diff intermediates (ex: PKB)
  • Stimulates PKB activity
  • PKB phosphorylates GSK3 so now its inhibited
  • Glycogen synthase = not phosphorylated
  • Addition of PP1 so net effect = dephosphorylation of glycogen synthase = activation of it
104
Q

What are the 3 effects of insulin on glucose uptake and glycogen synthesis in muscle?

A

stimulates glucose uptake, hexokinase activity, and glycogen synthesis

Biochem 311 (1 decks)

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