Glycogen and GSD

Question 1

An extended and branched polymer of glucose, with each granule having a molecular weight in excess of 2000 kDa

Answer 1

Glycogen

Question 2

Glucose residues are joined in a linear chain by

Answer 2

a-1,4 glycosidic bonds

Question 3

The branch points of glycogen, which occur, on average, every 10 or so residues, have an

Answer 3

a-1,6-glycosidic bond

Question 4

Composed of very long linear polymers of glucose, but in a B-1,4 linkage

Answer 4

Cellulose

Question 5

In plants, starch functions for energy storage, while cellulose has a

Answer 5

Structural role

Question 6

Represents one of the two basic forms in which the chemical energy derived from foods is stored

Answer 6

Glycogen

Question 7

The two largest reservoirs of glycogen in the body

Answer 7

Muscle and Liver

Question 8

Mobilized in the early phases of a fast, in order to maintain blood glucose levels

Answer 8

Liver Glycogen stores

Question 9

In most individuals, liver glycogen stores can meet this need for between

Answer 9

12-24 hours

Question 10

CANNOT contribute to the maintenance of blood glucose levels, but instead are utilized as a site specific energy source

Answer 10

Muscle glycogen stores

Question 11

The major intersection in the glucose metabolism road map

Answer 11

Glucose-6-phosphate

Question 12

Converts glucose-6-phosphate to glucose-1-phosphate

Answer 12

Phosphoglucomutase

Question 13

Glucose 1-phospate becomes the substrate for

-adds a UMP portion while releasing pyrophosphate (PPi)

Answer 13

UDP-glucose phosphorylase

Question 14

The resultant UDP-glucose is the immediate precursor in glycogen polymer extension, carried out by

Answer 14

Glycogen Synthase

Question 15

Polymerizes glucose residues by catalyzing the formation of the a-1,4-linkages

Answer 15

Glycogen synthase

Question 16

Addition of each glucose residue is coincident with release of its

Answer 16

UDP carrier

Question 17

Glycogen synthase cannot create branch structures, however. This task is the responsibility of the

Answer 17

Branching enzyme

Question 18

NOT a substrate for this enzyme

Answer 18

UDP-glucose

Question 19

Able to transfer a five- to eight-mer of a linear glycogen polymer to another glucose residue ‘upstream’ on the polymer chain, forming the alternative a-1,6 linkage

Answer 19

Branching Enzyme

Question 20

This creates a new polymer growing end and thus an additional substrate upon which glycogen synthase can act to elongate the

Answer 20

Glycogen Chain

Question 21

Cannot initiate polymer synthesis. It can only add to a pre-existing polymer

Answer 21

Glycogen Synthase

Question 22

Has several critical roles in the initiation of glycogen synthesis

Answer 22

Glycogenin

Question 23

The hydroxyl moiety of a tyrosine residue in glycogenin serves for the formation of the first

Answer 23

Glycosidic bond

Question 24

Importantly, this first glucose residue is attached not by glycogen synthase but by an enzymatic activity in

Answer 24

Glycogenin

Question 25

After the polymer is at least eight residues long, polymerization occurs via

Answer 25

Glycogen Synthase

Question 26

Apart from the ATP that is required to phosphorylate free glucose, one additional ATP is required for each glucose residue added to the

Answer 26

Polymer

Question 27

This ATP is consumed by -carries out the reaction UDP + ATP --> UTP + ADP

Answer 27

Nucleoside diphosphate kinase

Question 28

Echoing patterns in both glycolysis/gluconeogenesis and in fatty acid synthesis/B oxidation, glycogen breakdown is not simply the reverse of

Answer 28

Glycogen Synthesis

Question 29

Not an intermediate in glycogen breakdown

Answer 29

UDP-Glucose

Question 30

Importantly, it is in the breakdown of glycogen that the liver and muscle

Answer 30

Differ

Question 31

Glycogen breakdown begins at the many branch ends of the molecule, with the action of

Answer 31

Glycogen Phosphorylase

Question 32

Inorganic phosphate is recruited in this reaction, producing

Answer 32

Glucose-1-phosphate

Question 33

Glucose 1-phosphate is subsequently isomerized to glucose 6-phosphate by

Answer 33

Phosphoglucomutase

Question 34

The only enzyme the synthetic and degradative pathways share

Answer 34

Phosphoglucomutase

Question 35

In analogy to glycogen synthase, glycogen phosphorylase cannot attack the

Answer 35

a-1,6-linkage at branch points

Question 36

In fact, phosphorylase halts its progressive release of gluocse 1-phosphate molecules how many residues before a branch?

Answer 36

Four

Question 37

Branch removal is a 2-step process. The first step is catalyzed by the

Answer 37

Debranching enzyme (glucosyl (4:4) transferase)

Question 38

This enzyme transfers three of those four residues to another non-reducing end, in a single catalytic step, via conventional

Answer 38

a-1,4-linkages

Question 39

This leaves only one glucose residue in a

Answer 39

a-1,6-linkage

Question 40

The second step is catalyzed by amylo-(a-1,6)-glucosidase, which releases

Answer 40

Free glucose

Question 41

We will call this second enzymatic activity 'debranching enzyme' as well, because, in fact, both enzymatic activities dealing with breakdown of branch structures are present on

Answer 41

One polypeptide

Question 42

The result of glycogen mobilization in all tissues is the release, predominantly, of

Answer 42

Glucose-1-phosphate

Question 43

Able to remove the phosphate residue to liberate free glucose

Answer 43

Liver glucose-6-phosphatase

Question 44

Free glucose can in turn enter the circulation, thereby contributing to the maintenance of

Answer 44

Blood glucose

Question 45

In contrast, muscle lacks this phosphatase, so product gluose 6-phosphate is shunted directly into

Answer 45

Glycolysis for ATP production

Question 46

Remember that a modest quantity of free glucose is produced in muscle glycogen breakdown via the second step catalyzed by

Answer 46

De-branching enzyme

Question 47

While liver glycogen supplies serve to maintain blood glucose levels in the early stages of a fast, muscle glycogen does not, due to the absence of a muscle

Answer 47

Glucose-6-phosphatase

Question 48

What are the energy expenditures in mobilization of glycogen?

Answer 48

None

Question 49

Uses inorganic phosphate, not ATP, to produce glucose 1-phosphate

Answer 49

Glycogen phosphorylase

Question 50

The key enzymes targeted to regulate glycogen synthesis and breakdown are

Answer 50

Glycogen synthase and glycogen phosphorylase

Question 51

Hormonal regulation in the liver is mediated by

Answer 51

Insulin and glcucagon

Question 52

Hormonal regulation in the muscle is mediated by

Answer 52

Insulin and epinephrine

Question 53

Undergo covalent modifications that variously stimulate or inhibit their activity

Answer 53

Glycogen synthase and phosphorylase

Question 54

In exercising muscle, Ca2+ comes into play, and glycogen mobilization can reach very high rates in a matter of only a few

Answer 54

Seconds

Question 55

However, these changes can also be long lasting. Liver glycogenolysis is a process that may go on, uninterrupted, for

Answer 55

12 hours or more during fasting

Question 56

Contrasting the insulin/glucagon/epinephrine regulatory input is what we’ll call ‘local’ regulation via small molecule

Answer 56

Allosteric effectors

Question 57

During the early stages of a fast, and periods of muscle activity, the trend will be to

Answer 57

Activate the phosphorylase and inhibit the synthase

Question 58

For the energy poor state, what is the 1. ) Hormonal signal? 2. ) Intracellular signal?

Answer 58

1. ) GLucagon | 2. ) AMP

Question 59

Signal periods of muscle activity in skeletal muscle

Answer 59

Ca2+ and epinephrine

Question 60

The energy-poor hormonal signaling pathway in liver begins with the binding of glucagon to its

Answer 60

Membrane bound receptor

Question 61

The receptor activates an adenylate cyclase, causing an increase in intracellular

Answer 61

cAMP concentration

Question 62

cAMP in turn activates a

Answer 62

cAMP-dependent protein kinase

Question 63

Phosphorylates glycogen synthase-a, converting it to the inactive “b” form

Answer 63

cAMP-dependent protein kinase

Question 64

In fact, glycogen synthase is able to accept as many as -number of phosphatases determines degree of inhibition

Answer 64

9 phosphatases

Question 65

This same cAMP-dependent protein kinase also activates a second protein kinase, known as

Answer 65

Phosphorylase kinase

Question 66

In turn is able to convert inactive glycogen phosphorylase-b to the active (phosphorylated) a form

Answer 66

Phosphorylase kinase

Question 67

The net effect is the shut down of glycogen synthesis and the activation of

Answer 67

Glycogenolysis

Question 68

Nervous stimulation of muscle includes membrane bound receptor binding of

Answer 68

Epinephrine

Question 69

Nervous stimulation of muscle includes binding of epinephrine to its membrane-bound receptors as well as the release of sarcoplasmic stores of

Answer 69

Ca2+

Question 70

Epinephrine's stimulation of muscle glycogenolysis follows the cascade already described for

Answer 70

Glucagon

Question 71

Importantly, Ca++ binding to the calmodulin subunit of phosphorylase kinase stimulates its activity to phosphorylate

Answer 71

Glycogen phosphorylase

Question 72

This signaling can be done inthe absence of

Answer 72

cAMP

Question 73

As muscle relaxes, free intracellular Ca++ levels drop and the phosphorylase kinase is again deactivated by

Answer 73

Calmodulin

Question 74

Reverse the modifications made by phosphorylase kinase and the mobilization of glycogen halts once again

Answer 74

Cellular phosphatases

Question 75

On the local level, muscle glycogen phosphorylase is allosterically 1. ) Activated by (indicator of energy defecit)? 2. ) Inhibited by (indicator of energy abundance)?

Answer 75

1. ) AMP | 2. ) Phosphocreatine

Question 76

A good example of local regulation “trumping” hormonal regulation is shown here, where AMP can activate the

Answer 76

Unphosphorylated enzyme

Question 77

Conversely, the active, phosphorylated form can be locally inhibited by

Answer 77

ATP and Glucose-6-phosphate

Question 78

During energy-rich periods, and periods of muscle inactivity, the trend will be to

Answer 78

Activate the synthase and inhibit the phosphorylase

Question 79

What are the principal molecular signals of an energy rich state?

Answer 79

Insulin, G-6-P, Glucose, and ATP

Question 80

The energy-rich state is signaled by a high

Answer 80

Insulin to glucagon ratio

Question 81

Increasing this ratio stimulates glycogen synthesis over its

Answer 81

Degredation

Question 82

In liver and muscle, efficient insulin binding to its receptor activates a

Answer 82

Tyrosine Kinase

Question 83

This kinase in turn activates another kinase, whose ultimate target is

Answer 83

Protein Phosphatase 1 (PP1)

Question 84

Removes inhibitory phosphates from glycogen synthase (converting it back to the active "a" form), as well as removing the activating phosphate(s) from glycogen phosphorylase (converting it to the inactive "b" form)

Answer 84

PP1

Question 85

The net effect, therefore, of insulin signaling, is to

Answer 85

Activate glycogen synthase Inhibit glycogen phosphorylase

Question 86

In terms of local allosteric regulation, high levels of glucose 6-phosphate, signaling an energy rich state, allosterically

Answer 86

Activate glycogen synthase and inhibit glycogen phosphorylase

Question 87

Is also able to inhibit glycogen phosphorylase

Answer 87

ATP

Question 88

These effects are largely independent of the phosphorylation state of glycogen synthetase, and thus constitute a parallel regulatory mechanism that operates on local and short-term scales and is able to override

Answer 88

Hormonal input

Question 89

There are atleast 9 different deficiencies in glycogen metabolism. These are referred to as

Answer 89

Glycogen storage diseases or Glycogenoses