glycogen metabolism II

Question 1

regulation of glycogen metabolism is very important to

Answer 1

maintain blood sugar and provide energy to muscles

Question 2

rate limiting enzyme of glycogen synthesis

Answer 2

glycogen synthase

Question 3

rate limiting enzyme of glycogen degradation

Answer 3

glycogen phosphorylase

Question 4

glycogen synthase and glycogen phosphorylase (rate limiting enzymes of glycogen synthesis and degradation) are regulated by

Answer 4

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

Question 5

glycogen synthase exists in 2 forms

Answer 5

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

2. phosphorylated “b” form - inactive form

Question 6

glycogen synthase is phosphorylated by ______ and dephosphorylated by ______

Answer 6

glycogen synthase kinase (GSK)

protein phosphatase

Question 7

glycogen synthase kinase (GSK) is under the influence of

Answer 7

insulin

Question 8

allosteric regulation - power activator of glycogen synthase

Answer 8

glucose 6-phosphate

Question 9

glycogen phosphorylase exists in 2 forms

Answer 9

1. phosphorylated “a” form - active form (R relaxed state) - in liver
2. dephosphorylated “b” form - inactive form (T tense state) - in muscle

Question 10

glycogen phosphorylase is regulated by

Answer 10

several allosteric effectors (signal energy state of the cell)

reversible phosphorylation (responsive to hormones)

Question 11

liver and muscle forms of glycogen phosphorylase (GP) are products to 2 separate genes, they are called

Answer 11

isozymes

Question 12

liver and muscle forms of 
glycogen phosphorylase (GP) differ in their

Answer 12

sensitivities to regulatory molecules

Question 13

liver glycogen phosphorylase (GP) is inactivated by

Answer 13

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

Question 14

muscle glycogen phosphorylase (GP) is allosterically activated by

Answer 14

AMP (measure of low energy status of cell)

Question 15

allosteric regulation of liver glycogen phosphorylase (GP):

glucose binds to active site and

when glucose levels are high, no need for

Answer 15

stabilizes conformation in the inactive T state

glycogen breakdown (which would make more glucose)

Question 16

default form of liver glycogen phosphorylase is

Answer 16

“a” form or active form

Question 17

allosteric regulation of muscle glycogen phosphorylase (GP):

AMP bind to active site and

ATP and glucose-6-phosphate are

under normal physiological conditions, GP is inactive because of

Answer 17

stabilizes conformation of “b” in the active R state

negative allosteric regulators

inhibitory effect of ATP and gluc-6-phosphate

Question 18

default form of muscle glycogen phosphorylase is

Answer 18

“b” form or inactive form

Question 19

glycogenesis is favored in fed state:

blood glucose is ______

insulin is ______

cellular ATP is ______

Answer 19

high

high

high (signal of high energy)

Question 20

when glycogen synthesis is favored:

_______ form of glycogen synthase is dominant

_______ form of glycogen phosphorylase is dominant

Answer 20

dephosphorylated form (active)

dephosphorylated form (inactive)

Question 21

glycogenolysis is favored in fasting state and during exercise:

blood glucose is ______

glucagon is ______

cellular calcium is ______

AMP is ______

Answer 21

low

high

high (in exercising muscles)

high (from breakdown of ATP)

Question 22

when glycogen breakdown is favored:

_______ form of glycogen synthase is dominant

_______ form of glycogen phosphorylase is dominant

Answer 22

phosphorylated form (inactive)

phosphorylated form (active)

Question 23

Regulation of glycogen metabolism by insulin: glycogen synthase activation by insulin:

insulin binds to insulin receptor (receptor tyrosine kinase in muscle and liver) –> through signaling activates _____ –> PkB phosphorylates and activates _____ while phosphorylating and inactivating ______ –> PPI dephosphorylates ______ ______ (which is now activated) to proceed with glycogenesis

Answer 23

protein kinase B (PkB)

protein phosphatase I (PPI)

glycogen synthase kinase 3 (GSK3 typically phosphorylates glycogen synthase inactivating it)

glycogen synthase

Question 24

additional function of PkB

Answer 24

responsible for insertion of GLUT4 into plasma membrane

Question 25

regulation of glycogen metabolism: glycogen phosphorylase inactivation insulin binds to insulin receptor (receptor tyrosine kinase) through signaling activates ______ --> PkB phosphorylates and activates _______ which inactivates ______ ______ and ______ ______ --> making glycogen phosphorylase inactive (preventing glycogenolysis from occuring)

Answer 25

protein kinase B (PkB) protein phosphatase I (PPI) glycogen phosphorylase phosphorylase kinase (PK)

Question 26

active protein phosphatase I (PP1) dephosphoyrlates ________ and dephosphorylates _______

Answer 26

glycogen synthase (activates) glycogen phosphorylase (inactivates)

Question 27

mechanism of regulation by insulin: net result: glycogen synthesis via

Answer 27

activation of glycogen synthase and inactivation of glycogen phosphorylase

Question 28

type 2 diabetes: called: mutations in:

Answer 28

insulin resistance insulin receptor and/or downstream signaling proteins

Question 29

type 2 diabetes: down-regulation in receptor levels:

Answer 29

triggered by elevated insulin endocytosis and degradation of the insulin receptor defective receptors not replaced by translation

Question 30

normal blood glucose: prediabetic/at-risk: diabetes mellitus:

Answer 30

70-100 mg/dL (fasting) ; less than 140 (fed) 100-125 mg/dL (fasting) ; greater than 140 (fed) greater than 126 mg/dL (fasting) ; greater than 199 (fed)

Question 31

low blood sugar levels release

Answer 31

glucagon (acts on liver)

Question 32

muscle activity releases

Answer 32

epinephrine (effects are on muscle)

Question 33

glucagon and epinephrine are mediated by what type of receptors

Answer 33

GPCRs

Question 34

epinephrine and glucagon signal

Answer 34

glycogen breakdown

Question 35

phosphorylase kinase (PK) phosphorylates

Answer 35

glycogen phosphorylase to make it active

Question 36

phosphorylase kinase (inactive) --> _______ (partly active)

Answer 36

Ca 2+ (exercising muscle) | Ca2+ actually binds to calmodulin

Question 37

phosphorylase kinase (partly active) --> ________ (fully active)

Answer 37

PKA (which is activated by glucagon and epinephrine) phosphorylated form (phosphorylase a) (active form)

Question 38

regulation of glycogenolysis by glucagon and epinephrine: glycogen synthase inactivation ______ or ______ binds to GPCR and activates ______ ______ (which produces ______) --> cAMP activates ______ --> PkA inhibits _____ (by adding an inhibitor) and inhibits _____ (by phosphorylating) --> preventing assembling of glycogen (glycogenesis)

Answer 38

glucagon or epinephrine adenylyl cyclase cAMP PkA protein phosphatase 1 (PP1) glycogen synthase

Question 39

regulation of glycogenolysis by glucagon and epinephrine: glycogen phosphorylase activation: ______ or ______ binds to GPCR and activates ______ (which produces _____ ) --> cAMP activates ______ --> PkA phosphorylates and activates ______ which phosphorylates ______ and allows for _____ to take place

Answer 39

glucagon or epinephrine adenylyl cyclase cAMP PkA phosphorylase kinase (PK) glycogen phosphorylase (is now activated) glycogenolysis

Question 40

regulation of glycogenolysis by glucagon and epinephrine: net result:

Answer 40

glycogen breakdown (via inactivation of glycogen synthase and activation of glycogen phosphorylase)

Question 41

glucagon does not act on

Answer 41

muscle cells

Question 42

in liver, glucose 1-P converted to ______ and then to glucose by ______ which allows ______

Answer 42

glucose 6-P glucose-6-phosphatase free glucose to be released into blood stream

Question 43

_______ _______ is considered the glucose sensor in liver cells

Answer 43

glycogen phosphorylase

Question 44

GSD 0 defective enzyme: pathway affected:

Answer 44

glycogen synthase glycogenesis is affected patients cannot synthesize glycogen rely on glucose in diet

Question 45

GSD 1 disorder name: defective enzyme: pathway affected:

Answer 45

Von Gierke disease glucose 6-phosphatase inefficient release of free glucose into the bloodstream by the liver in gluconeogenesis and glycogenolysis

Question 46

GSD 2 disorder name: defective enzyme: pathway affected:

Answer 46

Pompe Disease acid maltase (used in lysosomal glycogen degradation) lysosomal glycogenolysis: accumulation of glycogen in lysosomes progressive muscle weakness and myopathy (including heart and skeletal muscle) ERT: recombinant human alpha-glucosidase delivered via IV infustion in children - effective

Question 47

GSD 3 disorder name: defective enzyme: pathway affected:

Answer 47

Cori disease debranching enzyme (alpha-1,6-glucosidase) glycogenolysis: glucose cleavage and release from branch point

Question 48

GSD 4 disorder name: defective enzyme: pathway affected:

Answer 48

anderson disease glucosyl (4:6) transferase glycogenesis: chain branching is limited death by 5 years of age

Question 49

GSD 5 disorder name: defective enzyme: pathway affected:

Answer 49

McArdle Disease muscle glycogen phosphorylase glycogenolysis: glucose 1-P release muscles break down (myoglobin in urine)

Question 50

GSD 6 disorder name: defective enzyme: pathway affected:

Answer 50

Hers disease liver glycogen phosphorylase glycogenolysis: glucose 1-P release low blood glucose levels (fairly benign)