Exam 2 Lecture 18 Glycogen Metabolism II

Question 1

regulation of glycogen metabolism is very important to maintain _ and provide _ to muscles

Answer 1

maintain blood sugar and provide energy to muscles

Question 2

the 2 key enzymes for glycogen metabolism are:

Answer 2

glycogen synthase and glycogen phosphorylase, the rate limiting steps of synthesis and degradation, respectively

Question 3

the 2 key enzymes for glycogen metabolism are regulated by _

Answer 3

allosteric regulators and by reversible phosphorylation (under the control of hormones)

Question 4

glycogen synthase exist in 2 forms which are:

Answer 4

1. non-phosphorylated “a” form-active form

2. phosphorylated “b” form-inactive form

Question 5

the 2 forms of glycogen synthase are phosphorylated by several kinases most importantly

Answer 5

glycogen synthase kinase (GSK)

Question 6

GSK is under the control of _

Answer 6

insulin

Question 7

allosteric regulation of glycogen synthase active form via

Answer 7

gluc-6-phosphate (poweful activator, stabilizes active form)

Question 8

in liver, glycogen synthase is in _ form

Answer 8

active “a” form; relaxed state

Question 9

in muscle, glycogen synthase is in _ form

Answer 9

inactive “b” form; tense state

Question 10

GP is regulated by:

Answer 10

1. several effectors (signal energy state of the cell)

2. reversible phosphorylation (responsive to hormones)

Question 11

low energy =

Answer 11

glycogen phosphatase (GP) to break down glycogen

Question 12

liver and muscle forms of GP are products of separate genes called _

Answer 12

isozymes

Question 13

liver and muscle forms of GP differ in their _

Answer 13

sensitivities to regulatory molecules

Question 14

liver GP form is inactivated by _ and unaffected by _

Answer 14

inactivated by free glucose (indicator of blood sugar levels) and unaffected by AMP

Question 15

muscle GP form is allosterically activated by _

Answer 15

AMP (measure of low energy status of cell)

Question 16

allosteric regulation of liver GP happens how?

Answer 16

glucose binds to default “a” form/active form and stabilizes conformation in the inactive T state

Question 17

when glucose levels are high =

Answer 17

no need for glycogen breakdown

Question 18

allosteric regulation of muscle GP happens how?

Answer 18

AMP binds to default “b” form/inactive form and stabilizes conformation of b in the active R state

Question 19

_ and _ stabilize the T state of muscle GP (normal physiological conditions) and are _ regulators

Answer 19

ATP and glucose-6P are negative allosteric regulators

Question 20

_ is a signal of low energy charge

Answer 20

AMP

Question 21

glycogenesis favored in _ state

Answer 21

fed state:

• blood glucose high
• insulin high
• cellular ATP high

Question 22

when glycogen synthesis is favored: dephosphorylated form of glycogen synthase = _ and the dephosphorylated form of glycogen phosphorylase = _

Answer 22

dephospho form of glycogen synthase = active and dephosph form of glycogen phosphorylase = inactive

Question 23

glycogenolysis favored in _ state

Answer 23

fasting state:

• cellular Ca2+ is high (in exercising muscle)
• AMP high (from breakdown of ATP)

Question 24

when glycogen breakdown is favored: phospho form of glycogen synthase = _ and the phospho form of glycogen phosphorylase = _

Answer 24

phospho form of glycogen synthase = inactive and phospho form of glycogen phosphorylase = active

Question 25

insulin receptor is what type of receptor?

Answer 25

tyrosine kinase

Question 26

high blood glucose regulation by insulin (Beta cells of pancreas) signaling cascade uses what 4 key proteins and the net result?

Answer 26

4 key proteins:

• GLUT4
• Protein Kinase B (PKB)
• Protein Phosphatase 1 (PP1)
• Glycogen Synthase Kinase 3 (GSK3)

net reult is glycogen synthesis via activation of glycogen synthase and inactivation of glycogen phosphorylase (both dephospho)

Question 27

PKB phosphorylates PP1 = _ and phosphorylates GSK3 = _

Answer 27

phospho PP1 = activated

phospho GSK3 = inactivated

Question 28

type 2 diabetes is called

Answer 28

insulin resistance

Question 29

low blood sugar levels release

Answer 29

glucagon (acts on liver)

Question 30

muscle activity releases

Answer 30

epinephrine (effects are on muscle)

Question 31

effects of hormones glucagon and epinephrine mediated via

Answer 31

G protein coupled receptors

Question 32

epinephrine and glucagon signal _

Answer 32

glycogen breakdown

Question 33

hormones initiate conversion of a single serine residue via? and what is converted?

Answer 33

phosphorylation of a single residue converts b to a. phosphorylation carried out by phosphorylase kinase (PK)

Question 34

low blood glucose regulation by glucagon (Alpha cells of pancreas) what are the key enzymes and 2nd messengers and the net result?

Answer 34

key enzymes and 2nd messengers:

• G protein
• adenylate cyclase (AC) and cAMP
• PKA
• PP1
• PK

net result is glycogen breakdown (via inactivation of glycogen synthase and activation of glycogen phosphorylase)

Question 35

glycogen breakdown “on switch”

Answer 35

glucagon

epinephrine

Question 36

glycogen breakdown “off switch”

Answer 36

when secretion of hormone stops; PK and GP are dephospho and inactivated

Question 37

which glucose transporter is in the liver?

Answer 37

GLUT2

Question 38

glucagon does not act on muscle bc

Answer 38

no glucagon receptors in muscle

Question 39

in liver, glucose-1P converted to glucose-6P and then to _ via

Answer 39

into Glu via glucose-6-phosphatase; free glucose released into blood stream

Question 40

myocytes in skeletal and cardiac muscle lack glucose-6-phosphatase thus

Answer 40

cannot hydrolyze glucose-6P. uses glucose-6P to generate energy via glycolysis and TCA cycle

Question 41

glycogen phosphorylase is the _ in liver cells

Answer 41

glucose sensor; response is immediate

Question 42

if you were to infuse glucose into the blood stream what happens to enzymatic activity of phosphorylase and synthase

Answer 42

since phosphorylase is a glucose sensor in liver cells and its response is immediate, phosphorylase is inactivated and glycogen synthase is activated in the liver

Question 43

what are the characteristics of glycogen storage diseases?

Answer 43

• autosomal recessive
• disorders that effect breakdown lead to hepatomegaly and hypoglycemia (inability to maintain blood sugar)
• disorders that affect synthesis (pts depend on glucose rather than glycogen)

Question 44

GSD 0:

Answer 44

-deficiency in glycogen synthase (pts cannot synthesize glycogen rely on glucose in diet)

Question 45

GSD1a/Von Gierke disease:

Answer 45

• deficiency in glucose-6-phosphatase

- inefficient release of free glucose into the bloodstream by the liver in gluconeogenesis and glycogenolysis

Question 46

GSD II/Pompe Disease

Answer 46

• deficient in acid maltase (aka alpha-glucosidase) use in lysosomal glycogen degradation pathway
• progressive muscle weakness and myopathy (including heart and skeletal muscle)
• enzyme replacement therapy via recombinant human alpha-glucosidase

Question 47

GSD III/Cori Disease

Answer 47

-deficiency in alpha-1,6-glucosidase (debranching enzyme)

Question 48

GSD IV/Anderson Disease

Answer 48

• deficiency in glucosyl (4:6) transferase (branching enzyme)
• longer chains glucose fewer branches causes enlargement of liver and spleen

Question 49

GSD V/McArdle Disease

Answer 49

deficiency in muscle glycogen phosphorylase

Question 50

GSD VI/Hers Disease

Answer 50

• deficiency in liver glycogen phosphorylase

- prevents glycogen breakdown in liver ie enlargement