Mitsouras: Glycogenesis

Front 1

When does glycogenesis occur?

Back 1

When glucose is abundant; fed state

Front 2

Where are the two locations excess glucose is stored?

Back 2

Fat, Glycogen

Front 3

Where does glycogen storage occur?

Back 3

Liver, muscle

Front 4

How does glycogenesis prevent hyperglycemia?

Back 4

Sequesters glucose

Front 5

What transporter takes glucose into liver?

Back 5

GLUT2

Front 6

What transporter takes glucose into muscle?

Back 6

GLUT4

Front 7

What transporter is activated by insulin?

Back 7

GLUT4 is stimulated by insulin

Front 8

What does insulin stimulate in the liver and muscle?

Back 8

Glycogenesis

Front 9

What is Pompe's Disease?

Back 9

A glycogen storage disease

Front 10

What is a glycogen storage disease?

Back 10

Enzymatic deficiency is glycogenesis or glycogenolysis

Front 11

What cells are affected in glycogen storage diseases?

Back 11

liver, muscle or both

Front 12

What are the symptoms of glycogen storage diseases?

Back 12

hypoglycemia, cardiomegaly, hepatomegaly, muscle weakness

*symptoms vary in severity

Front 13

What processes are stimulated by glucagon?

Back 13

Glycogenolysis, Gluconeogenesis

Front 14

What processes are stimulated by insulin?

Back 14

Glycolysis, Glycogenesis

Front 15

Do glycogen synthesis and degradation utilize the same enzymes?

Back 15

No

Front 16

Are the pathways independently regulated? Reciprocally regulated?

Back 16

Both reciprocally and independently regulated

Front 17

How is futile cycling prevented between glycogenesis and glycogenolysis?

Back 17

Reciprocal regulation

Front 18

What reciprocal regulation occurs in the fed state?

Back 18

Fed state uses insulin, which turns on glycogenesis and turns off glycogenolysis
This prevents newly synthesized glycogen from being degraded

Front 19

What occurs in fasting state?

Back 19

Glucagon is used to signal glycogenolysis and stops glycogenesis to prevent the glucose from the degraded glycogen from being anabolized into glycogen

Front 20

What is the net producer of glucose during fasting and starvation?

Back 20

Liver

Front 21

What is the primary function of glycogenolysis and glycogenesis?

Back 21

Blood glucose homeostasis

Front 22

What happens with glycolysis and glycogenesis during fasting and starvation?

Back 22

Glycolysis off to prevent the liver from using glucose produced in glycogenolysis

Glycogenesis off so that glucose produced is not stored and can be used as fuel

Front 23

What is glycogen?

Back 23

a glucose polymer of 10,000-40,000x

Front 24

What are the effects of glycogen branching?

Back 24

1. Increase solubility
2. Provide extra sites for adding and removing glucose residues

Front 25

How often does glycogen branch?

Back 25

Every 8-12 residues

Front 26

What type of bonds are found in the linear chains of glycogen?

Back 26

alpha(1,4)

Front 27

What type of bonds are found at glycogen branchpoints?

Back 27

alpha(1,6)

Front 28

Where do glycogen degredation and synthesis occur?

Back 28

Cytoplasm

Front 29

Describe the alpha(1,4) bond:

Back 29

Anabolic glucose (one being added) attaches via a glycosidic bond from its C1 to the OH group on C4 of the last glycogen on the chain

Front 30

Which serves as the reducing end in glycogenesis?

Back 30

The free OH at C-1= free oxygen can be oxidized= reducing end

Front 31

How many reducing ends does each glucose molecule have?

Back 31

1, from the OH at C-1

Front 32

What type of bond occurs between the free OH group of glycogen and the C-1 of the incoming glucose?

Back 32

glycosidic

Front 33

Where is the reducing end?

Back 33

C-1 carbon with a free OH

Front 34

Where are the non-reducing ends? What do they do?

Back 34

There are many;
They serve as the sites for addition or removal of glucose

Front 35

How is glucose added to glycogen?

Back 35

UDP-glucose is added to the non-reducing ends of glycogen

Front 36

What enzyme creates the alpha(1,4) bonds?

Back 36

glycogen synthase

Front 37

What enzyme creates the alpha(1,6) bonds?

Back 37

branching enzyme

Front 38

What is the overall reaction for glycogen synthesis?

Back 38

glycogen(n) + UDP-glucose= glycogen (n+1) + UDP

Front 39

What is the substrate for glycogenesis?

Back 39

UDP-glucose

Front 40

What molecule is an activated carrier?

Back 40

UDP-glucose

Front 41

Where is the energy for the glycosidic bond formation from?

Back 41

The activation carrier, UDP-glucose

Front 42

How does UDP-glucose provide the energy for the glycosidic bond formation?

Back 42

Hydrolysis of the energy-rich bond in activated carrier

Front 43

Where does the UDP attach to the glucose?

Back 43

To the OH group of C1

Front 44

What is the anomeric C?

Back 44

C1 with free OH

Front 45

What is the first step of UDP-glucose formation?

Back 45

1. Glucose trapped in cell by glucokinase/hexokinase (ATP used)= forms Glucose 6P
2. Glucose 6P becomes Glucose 1P by phosphoglucomutase (reversible)
3. Glucose 1P + UTP= UDP-glucose + PPi via UDP-glucose pyrophosphorylase and Mg2+

Front 46

How is the formation of UDP-glucose driven forward?

Back 46

Removal of the other product, PPi via pyrophosphatase to form 2Pi

Front 47

What enzyme drives the conversion of Glucose to Glucose 6P?

Back 47

hexokinase (all cells but liver and pancreas)
glucokinase (liver, pancreas)

Front 48

What enzyme drives the conversion of Glucose 6P to glucose 1P?

Back 48

phosphoglucomutase

Front 49

What enzyme drives the conversion of glucose 1P to UDP-glucose?

Back 49

UDP-glucose phyrophosphorylase (and Mg2+ as cofactor)

Front 50

What enzyme removes PPi to drive the reversible reaction between Glucose 1P and UTP toward the formation of UDP-glucose?

Back 50

Removal of PPi by pyrophosphatase, which forms 2Pi

Front 51

What reaction of UDP-glucose synthesis is shared with the galactose metabolism pathway?

Back 51

Conversion of Glucose 6P to Glucose 1P

Front 52

What reaction of the UDP-glucose synthesis is shared with glycolysis?

Back 52

Conversion of glucose to glucose 6P

Front 53

How does galactose form Glucose 1P?

Back 53

Galactose in the liver
1. Galactose to Galactose 1P by galactokinase
2. Galactose 1P to Glucose 1P by galactose-1P-uridyltransferase

Front 54

What are the potential end products of Glucose 1P?

Back 54

1. Glycolysis via Glucose 6P
2. Gluconeogenesis via Glucose 6P
3. UPD-glucose via UDP-glucose pyrophosphorylase
4. UPD-glucose when Glucose 1P + UDP-Galactose via UPD-hexose-4-epimerase

Front 55

What is UDP-hexose-4-epimerase?

Back 55

Forms UDP-Glucose when Glucose 1P + UPD-galactose

Front 56

What does glycogen synthase do?

Back 56

catalyzes bond bw C1 of incoming glucose and non-reducing end of glycogen

Front 57

How long does a glycogen chain have to be to serve as a primer?

Back 57

4 glucose residues long

Front 58

What does glycogen synthase require for elongation?

Back 58

a primer

Front 59

What are the possible primers for glycogen synthase?

Back 59

1. Existing glycogen molecule (at lease 4 glucose residues long)
2. Glucosyl chain attached to glycogenin

Front 60

What performs de novo chain synthesis for glycogen?

Back 60

Glycogenin

Front 61

What does glycogenin do?

Back 61

autocataylzes at a tyrosine residue, autocatalyzes again until it is long enough to be used as a primer for glycogen synthase

Front 62

What forms the core of glycogen molecules?

Back 62

Glycogenin

It remains associated to the growing glycogen molecules

Front 63

Approx how many glucoses are added to the glycogen chain before branching?

Back 63

11

Front 64

What enzyme catalyzes the branching of glycogen?

Back 64

branching enzyme

Front 65

What type of bonds are formed in branching?

Back 65

alpha(1,6)

Front 66

How does branching enzyme work?

Back 66

Net transfer of 6-8 glucose residues from non-reducing end to internal position and creation of an alpha(1,6) bond

Hydrolysis of alpha(1,4) and transfer with alpha (1,6) formation to produce another non-reducing end

Front 67

What is the alpha(1,6) formed by branching enzyme between?

Back 67

glucose in an internal position and terminal glucose of fragment

Front 68

What is the energy requirement per glucose added to glycogen?

Back 68

1 ATP
1 UTP

Front 69

Where does the ATP used in glycogen formation come from?

Back 69

Glycogenesis occurs in fed state, so energy is from oxidation of glucose

Front 70

When is ATP used in glycogenesis?

Back 70

Conversion of Glucose to Glucose 6P by hexokinase or glucokinase

Front 71

When is UTP used in glycogenesis?

Back 71

In the conversion of Glucose-1P to UDP-Glucose

Front 72

How is glycogenesis hormonally regulated in the fed state?

Back 72

Insulin activates protein phosphatase 1, which removes the phosphate from glycogen synthase and turns glycogen synthase on, thus turning on glycogenesis

Front 73

How is glycogenesis allosterically regulated in the fed state?

Back 73

1. Glucose 6P turns glycogen synthase on
2. Glucose turns protein phosphatase 1 on

Front 74

How is glycogeneis hormonally regulated in the fasting state?

Back 74

1. Glucagon activates protein kinase A, which phosphorylates glycogen synthase and turns it off, thus turning glycogenesis off

Front 75

What is the active form of glycogen synthase?

Back 75

Dephosphorylated

Front 76

What turns glycogen synthase off?

Back 76

Phosphorylation by protein kinase A, which is activated by glucagon

Front 77

What processes are activated by insulin?

Back 77

1. Stimulates glucose uptake in muscle and adipose
2. Stimulates glycogen synthesis in muscle and liver
3. Stimulates synthesis of TAGs in adipose
4. Stimulates synthesis of fatty acids in liver

Front 78

What processes are inhibited by insulin?

Back 78

1. Gluconeogenesis
2. Glycogenolysis
3. Lipolysis

Front 79

Where is insulin secreted from?

Back 79

Beta cells in pancreas

Front 80

What stimulates secretion of insulin from the beta cells of the pancreas?

Back 80

Glucose

Front 81

How is insulin formed?

Back 81

1. Synthesized as preproinsulin
2. Cleaved by proteolysis to give proinsulin
3. Pro-insulin becomes C-peptide and insulin

Front 82

Where is insulin stored?

Back 82

In the cytoplasm of beta-cells