Glycogenolysis And Glycogenesis 2

Front 1

How is glycogen degraded?

Back 1

- phosphorolysis by glycogen phosphorylase and debrancing enzyme
- other enzymes: debranching enzymes, phophoglucomutase, and amylase

Front 2

How does glycogen phosphorylase break down glycogen?

Back 2

- it breaks it one at a time (alpha 1 to 4) by removing a glucose at the nonreducing end
- makes Glucose 1-Phosphate
- energy is preserved in the phosphoryl grp

Front 3

What does debranching enzyme do?

Back 3

- it transfer branches to nonreducing end so glycogen phosphorylase keeps breaking them down

Front 4

What happens to Glucose 1-Phosphate?

Back 4

- G1P to G6P by phophoglucomutase (donates phophate grp then takes it back after positions switch)
- G1P turned into G6P and then glucose by glucose 6-phosphatase

Front 5

How does G6P get to blood?

Back 5

- by hydrolysis of G6P by G6Pase of the endoplasmic reticulum
- G6P is hydrolyzed to glucose by G6Pase that is an integral protein in membrane in ER
- glucose leaves hepatocyte through GLUT2 to the blood

Front 6

Glycogen synthesis

Back 6

- catalyzed by hexokinase I through IV
- other enzymes: phophoglucomutase, UDP-glucose pyrophosphorylase, glycogen synthase, and glycogen branching enzyme

Front 7

Sugar Nucleotides for biosynthetic reactions (UDP-Glucose)

Back 7

- formation is irreversible
- nucleotide proved additional binding energy for enzymes
- UMP is a good leaving group, facilitates nucleophilic attack
- tagging of the hexoses to set aside in a pool for glycogen synthesis or from hexose phophates for glycolysis
- breakdown of sugar phosphate to 2 phosphates and NDP-sugar

Front 8

How does glycogen synthesis start?

Back 8

- starts with G6P (can come free glucose catalyzed by hexokinase)
- G6P -> G1P by phophoglucomutase
- G1P -> UPD-glucose by UDP-glucose pyrophophorylase
- UPD-glucose donates glucose residue in rxn by glycogen sythase to nonreducing end of glycogen

Front 9

Glycogenin

Back 9

- initiates new glycogen chain
- a primer
- transfer a glucose residue from UDP-glucose to Tyr of glycogenin
- glucose adds from there for six times

Front 10

Regulatory mechanisms are shaped by what?

Back 10

- need to maximize efficiency of fuel utilization by preventing simultaneous operation of pathwyas in opposite directions
- partitioning of metabolites between pathways
- use the best suited fuel at hand
- shut down pathways which accumulate product

Front 11

Which is a more sensitive indicator of a cell's energetic state, ATP or AMP?

Back 11

- AMP (relative change in AMP is much greater than ATP)

Front 12

Protein kinase

Back 12

- phosphorylates by adding phosphate group to protein substrate from ATP

Front 13

Phophoprotein phophatase

Back 13

- dephosphorylates by removing phosphoryl group as Pi

Front 14

What are the 3 enzymes that are regulated in glycolysis?

Back 14

1.) hexokinase
2.) phophofructokinase-1
3.) pyruvate kinase

Front 15

Hexokinase regulation

Back 15

- 3rd bypass in gluconeogenesis
- hexokinase I through IV
- liver hexokinase IV is not inhibitied by Glucose 6-Phosphate

Front 16

What happens to hexokinase I activity when glucose increases?

Back 16

- it is inhibited because it is totally saturated, already at Vmax

Front 17

What happens to hexokinase IV activity when glucose concentration increases?

Back 17

- activity continues to increase because it is not totally saturated, making more G6P

Front 18

Hexokinase IV activity rises at about what glucose concentration?

Back 18

- 5 mM

Front 19

G6P inhibits what hexokinases?

Back 19

- it inhibits hexokinase I-III, but not hexokinase IV

Front 20

Glucose needs to be increased or decreased in order to activate hexokinase IV?

Back 20

increased

Front 21

What happens to hexokinase IV when glucose is low?

Back 21

- it is inhibited until glucose is at 5 mM

Front 22

What is the protein inhibitor of hexokinase IV?

Back 22

- a nuclear binding protein that draws hexokinase IV into the nucleus when F6P increases, inhibiting hexokinase IV

Front 23

Regulation of phosphofructokinase-1

Back 23

- 2nd bypass
- under complex allosteric regulation

Front 24

What happens to PFK-1 when ATP increases?

Back 24

- it is inhibited by binding to an allosteric site and lowering the affinity of PFK-1 for F6P

Front 25

What stimulates PFK-1?

Back 25

- decrease in ATP
- increase in AMP and ADP

Front 26

PFK-1 is inhibited when ATP is low or high?

Back 26

high (negative regulator)

Front 27

PFK-1 is stimulated when ATP is low or high

Back 27

low (positive regulator)
- PFK-1 functions at a high rate when F6P is low

Front 28

When ATP is low, what happens to glycolysis?

Back 28

glycolysis increases

Front 29

When ATP is high, what happens to glycolysis?

Back 29

- it is inhibited

Front 30

What stimulates PFK-1?

Back 30

- AMP, ADP
- fructose 2,6-bisphosphate

Front 31

Pyruvate Kinase Regulation

Back 31

- 1st bypass
- different isoforms in muscle and liver
- liver form inhibited by phosphorylation

Front 32

What enzyme phosphorylates the L form and doing what to it?

Back 32

- cAMP-dependent protein kinase (PKA) phosphorylates PK
- inactivating it

Front 33

What enzyme dephosphorylates the L form and doin what to it?

Back 33

- protein phosphatase (PP) dephosporylates PK
- activating it

Front 34

What does glucagon do to PKA?

Back 34

- it activates PKA, phosphorylating PK, inactivating it so glucose is exported to other tissues than the liver

Front 35

What lvl does glucagon needs to be in order to activate PK?

Back 35

- it needs to be low in order to PP to dephosphorylate PK, therefore activating it

Front 36

What do ATP, aCoA, and FAs do to pyruvate kinase?

Back 36

- a high ATP, aCoA, and FAs (signs of high fuel) inhibit pyruvate kinase

Front 37

What does F16BP do to pyruvate kinase?

Back 37

- an increase in F16BP activates PK

Front 38

Gluconeogenesis Regulation Points

Back 38

1.) pyruvate carboxylase and pyruvate dehydrogenase complex
2.) PFK-1 and FBPase-1

Front 39

What does pyruvate dehydrogenase complex do?

Back 39

- converts pyruvate to aCoA for TCA cycle

Front 40

What does pyruvate carboxylase do?

Back 40

- converts pyruvate to oxaloacetate to start gluconeogenesis

Front 41

What do FAs and aCoA do to pyruvate dehydrogenase complex?

Back 41

- FAs inhibit PDC and activates pyruvate carboxylase

Front 42

What happens to fructose 1,6-bisphosphatase-1 (FBPase-1) when AMP is high?

Back 42

- FBPase-1 is inhibited when AMP is increased

Front 43

What happens to PFK-1 when there is an increase in AMP and ADP?

Back 43

- PFK-1 is increased (glycolysis)

Front 44

What happens to PFK-1 when citrate and ATP are increased?

Back 44

- PFK-1 is decreased (gluconeogenesis)

Front 45

What happens to glycogen phosphorylase when AMP and ADP are high?

Back 45

- it is increased, to make more glucose for energy

Front 46

What does ATP do to glycolysis?

Back 46

- ATP inhibits PFK-1, there for inhibits glycolysis

Front 47

What does ADP do to glycolysis?

Back 47

- ADP stimulates PFK-1, therefore activates glycolysis

Front 48

What does citrate do to glycolysis?

Back 48

- citrate inhibits PFK-1, therefore inhibits glycolysis

Front 49

What is Fructose 2,6-bisphosphate?

Back 49

- an allosteric effector for PFK-1 and FBPase-1
- lvl of F26PB reflect glucagon

Front 50

What happens when F26BP binds to PFK-1?

Back 50

- it increases PFK-1 affinity for F6P, and decrease affinity for ATP and citrate

Front 51

What happens to PFK-1 when there is no F26BP?

Back 51

- PFK-1 is inactive

Front 52

What happens to glycolysis when there is F26BP?

Back 52

- glycolysis is stimulated by F26BP

Front 53

What happens to the affinity of PFK-1 for F6P when there is no F26PB?

Back 53

- a decrease in affinity for F6P

Front 54

What happens to FBPase-1 when there is no F26BP?

Back 54

- it is stimulated

Front 55

What does F26BP do to FBPase-1?

Back 55

- it inhibits it by making it more sensitive to inhibition like AMP

Front 56

FBPase-1 goes to glycolysis or gluconeogenesis?

Back 56

gluconeogenesis

Front 57

How is F26BP formed?

Back 57

- by phosphorylation of F6P by PFK-2

Front 58

How is F26BP broken down?

Back 58

- by FBPase-2

Front 59

What does glucagon do to F26BP?

Back 59

- glucagon decreases F26BP (inhibits glycolysis and stimulates gluconeogenesis)

Front 60

What happens to PFK-2/FBPase when it is phosphorylated?

Back 60

- PFK-2 is inactivated
- FBPase-2 is activated

Front 61

What happens to PFK-2/FBPase when it is dephosphorylated?

Back 61

- PFK-2 is activated
- FBPase-2 is inactivated

Front 62

What enzyme phosphorylates PFK-2/FBPase-2?

Back 62

- cAMP-dependent protein kinase (PKA)

Front 63

What enzyme dephosphorylates PFK-2/FBPase-2?

Back 63

- phophoprotein phosphatase

Front 64

What does insulin do to F26BP?

Back 64

- it increases F26BP (stimulates glycolysis)

Front 65

Glycogen breakdown

Back 65

- catalyzed by glycogen phophorylase
- breakdown of glycogen can have different consequences in liver vs. muscle

Front 66

Glucagon acts on what organ?

Back 66

liver

Front 67

epinephrine acts on what organ?

Back 67

muscle

Front 68

How does epinephrine act in a myocyte?

Back 68

- epinephrine activates GTP-binding protein, increases cAMP which increases PKA
- increase PKA activates phophorylase b kinase, which activates glycogen phophorylase a
- glycogen phophorylase a breaks down glycogen to G1P which can go to glycolysis for muscle contraction

Front 69

How does glucagon act in the hepatocyte?

Back 69

- glucagon activates GTP-binding protein that increases cAMP
- activates PKA, phophorylase b kinase, glycogen phophorylase a
- which turns glycogen to G1P, which can be made to glucose for blood

Front 70

What activates glycogen breakdown?

Back 70

- increase in Ca2+ (muscle contraction)
- increase in AMP

Front 71

What happens to glycogen phosphorylase when ATP is high?

Back 71

- it is decreased

Front 72

Glycogen phophorylase is activated when phosphorylated or dephosphorylated?

Back 72

- when it is phosphorylated

Front 73

What happens to glycogen phosphorylase when glucose enters hepatocyte?

Back 73

- exposes phosphorylated Ser

Front 74

What enzyme dephosphorylates glycogen phsophorylase?

Back 74

- phophorylase a phosphatase (PP1), inactivating it

Front 75

What does insulin do to phosphorylase a phophatase?

Back 75

- it stimulates PP1 (slows glycogen breakdown, when glucose is high)

Front 76

What does phosphorylase b kinase do to glycogen phosphorylase?

Back 76

- it phosphorylates phosphorylase, activating it

Front 77

What removes phophoryl groups from phosphorylase?

Back 77

- phosphorylase a phosphatase (PP1), inactivating it

Front 78

What form of phosphorylase predominates in resting muscle?

Back 78

phosphorylase b

Front 79

What does epinephrine do to phosphorylase?

Back 79

- epinephrine activates phosphorylase

Front 80

What does glucagon do to phosphorylase?

Back 80

- glucagon activates phosphorylase

Front 81

Glycogen synthesis regulation

Back 81

- catalyzed by glycogen synthase

Front 82

What inactivates glycogen synthase?

Back 82

- glycogen synthase kinase 3

Front 83

What activates glycogen synthase?

Back 83

- phosphoprotein phosphatase

Front 84

What is glycogen synthase a?

Back 84

- the active form
- unphophorylated

Front 85

What is glycogen synthase b?

Back 85

- the inactive unless G6P is present
- phosphorylated

Front 86

What is glycogen synthase kinase 3?

Back 86

- adds phophoryl grps to 3 Ser residues near C-terminal fo glycogen synthase, strongly inactivating glycogen synthase

Front 87

What effects the insulin have on GSK3?

Back 87

- insulin inhibits GSK3

Front 88

What happens to glycogen synthase when GSK3 is inhibited?

Back 88

- it is activated because it is not phosphorylated by GSK3

Front 89

What does phosphoprotein phophatase (PP1) do to glycogen synthase?

Back 89

- PP1 activates glycogen synthase

Front 90

What does insulin do to PP1?

Back 90

- insulin stimulates PP1 (activating glycogen synthase)

Front 91

What does glucagon and epinephrine do to PP1?

Back 91

- glucagon and epinephrine inhibits PP1 (inactivating glycogen synthase) by dissociating PP1 from glycogen synthase

Front 92

What does G6P do to PP1?

Back 92

- G6P stimulates PP1 (activating glycogen synthase)

Front 93

What does glucose do to PP1?

Back 93

- it stimulate it (activating glycogen synthase)

Front 94

GSK3 requires priming by what enzyme?

Back 94

casein kinase II (CKII)

Front 95

What is the Pseudosubstrate of GSK3?

Back 95

when GSK3 folds into priming site and active site making it inaccessible and inhibiting it

Front 96

What does protein kinase (PKB) do to GSK3?

Back 96

- it phosphorylates GSK3 making it inactive

Front 97

What does insulin do to protein kinase (PKB)

Back 97

- it activates it

Front 98

What happens to PP1 when glycogen phosphorylase is activated?

Back 98

- it is inhibited, deactivating glycogen synthase

Front 99

What enzyme is a glucose sensor?

Back 99

glycogen phophorylase

Front 100

What enzyme is a G6P sensor?

Back 100

glycogen synthase

Front 101

Phosphoprotein phosphatase 1 (PP1)

Back 101

- dephosphorylates glycogen phosphorylase, glycogen synthase, and phosphorylase kinase

Front 102

How does insulin stimulate glycogen synthesis?

Back 102

by activating PP1 and inactivating GSK3

Front 103

What does PKA do to PP1?

Back 103

- it phosphorylates PP1 making PP1 inactive

Front 104

Glycogen-targeting protein (Gm)

Back 104

- bind other proteins like PP1 to glycogen particles
- can be phosphorylated in 2 different positions in response to insulin or epinephrine

Front 105

What does insulin do to PP1?

Back 105

- insulin activates PP1, which dephosphorylates phosphorylase kinase, glycogen phophorylase, and glycogen synthase
- glycogen synthesis

Front 106

What does epinephrine do to PKA?

Back 106

- epinephrine activates PKA, which phosphorylates site 2 of Gm
- this dissociates PP1 from glycogen preventing it's access to glycogen phosphorylase and glycogen synthase
- decrease glycogen synthesis
- glycogen breakdown

Front 107

When there is a high blood sugar, what happens to glycogen?

Back 107

- glycogen is synthesized

Front 108

What happens to GSK3 when insulin is increased?

Back 108

- GSK3 is inactived by insulin, which activates PP1 (glycogen synthesis)

Front 109

What happens to glycogen phophorylase when PP1 is active?

Back 109

- PP1 inactivates glycogen phophorylase, which inactivates phosphorylase kinase by dephosphorylating both (decrease in glycogen breakdown)

Front 110

What happens to hexokinase IV when glucose enters through GLUTZ?

Back 110

- it dissociates hexokinase IV from its nuclear regulator protein
- hexokinase phosphorylates glucose (glycolysis and glycogen synthesis)

Front 111

What happens to PKA when there is a low blood glucose?

Back 111

- increases PKA, which phosphorylates and activates phophorylase kinase, activating glycogen phophorylase
- phosphorylates and inactivates glycogen synthase, decreasing glycogen synthesis
- phosphorylates PFK-2/PBPase-2, activating FBPase-2, inactivating PFK-2, decreasing F26BP and PFK-1
- phosphorylates and inactivates glycolytic pyruvate kinase, increases G6P by glycogen breakdown and by gluconeogenesis (decreasing glycolysis)

Front 112

Can muscle go through gluconeogenesis?

Back 112

- no, it uses its stored glycogen