Exam 2 Lecture 18 Glycogen Metabolism II Flashcards
regulation of glycogen metabolism is very important to maintain _ and provide _ to muscles
maintain blood sugar and provide energy to muscles
the 2 key enzymes for glycogen metabolism are:
glycogen synthase and glycogen phosphorylase, the rate limiting steps of synthesis and degradation, respectively
the 2 key enzymes for glycogen metabolism are regulated by _
allosteric regulators and by reversible phosphorylation (under the control of hormones)
glycogen synthase exist in 2 forms which are:
- non-phosphorylated “a” form-active form
2. phosphorylated “b” form-inactive form
the 2 forms of glycogen synthase are phosphorylated by several kinases most importantly
glycogen synthase kinase (GSK)
GSK is under the control of _
insulin
allosteric regulation of glycogen synthase active form via
gluc-6-phosphate (poweful activator, stabilizes active form)
in liver, glycogen synthase is in _ form
active “a” form; relaxed state
in muscle, glycogen synthase is in _ form
inactive “b” form; tense state
GP is regulated by:
- several effectors (signal energy state of the cell)
2. reversible phosphorylation (responsive to hormones)
low energy =
glycogen phosphatase (GP) to break down glycogen
liver and muscle forms of GP are products of separate genes called _
isozymes
liver and muscle forms of GP differ in their _
sensitivities to regulatory molecules
liver GP form is inactivated by _ and unaffected by _
inactivated by free glucose (indicator of blood sugar levels) and unaffected by AMP
muscle GP form is allosterically activated by _
AMP (measure of low energy status of cell)
allosteric regulation of liver GP happens how?
glucose binds to default “a” form/active form and stabilizes conformation in the inactive T state
when glucose levels are high =
no need for glycogen breakdown
allosteric regulation of muscle GP happens how?
AMP binds to default “b” form/inactive form and stabilizes conformation of b in the active R state
_ and _ stabilize the T state of muscle GP (normal physiological conditions) and are _ regulators
ATP and glucose-6P are negative allosteric regulators
_ is a signal of low energy charge
AMP
glycogenesis favored in _ state
fed state:
- blood glucose high
- insulin high
- cellular ATP high
when glycogen synthesis is favored: dephosphorylated form of glycogen synthase = _ and the dephosphorylated form of glycogen phosphorylase = _
dephospho form of glycogen synthase = active and dephosph form of glycogen phosphorylase = inactive
glycogenolysis favored in _ state
fasting state:
- cellular Ca2+ is high (in exercising muscle)
- AMP high (from breakdown of ATP)
when glycogen breakdown is favored: phospho form of glycogen synthase = _ and the phospho form of glycogen phosphorylase = _
phospho form of glycogen synthase = inactive and phospho form of glycogen phosphorylase = active
insulin receptor is what type of receptor?
tyrosine kinase
high blood glucose regulation by insulin (Beta cells of pancreas) signaling cascade uses what 4 key proteins and the net result?
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)
PKB phosphorylates PP1 = _ and phosphorylates GSK3 = _
phospho PP1 = activated
phospho GSK3 = inactivated
type 2 diabetes is called
insulin resistance
low blood sugar levels release
glucagon (acts on liver)
muscle activity releases
epinephrine (effects are on muscle)
effects of hormones glucagon and epinephrine mediated via
G protein coupled receptors
epinephrine and glucagon signal _
glycogen breakdown
hormones initiate conversion of a single serine residue via? and what is converted?
phosphorylation of a single residue converts b to a. phosphorylation carried out by phosphorylase kinase (PK)
low blood glucose regulation by glucagon (Alpha cells of pancreas) what are the key enzymes and 2nd messengers and the net result?
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)
glycogen breakdown “on switch”
glucagon
epinephrine
glycogen breakdown “off switch”
when secretion of hormone stops; PK and GP are dephospho and inactivated
which glucose transporter is in the liver?
GLUT2
glucagon does not act on muscle bc
no glucagon receptors in muscle
in liver, glucose-1P converted to glucose-6P and then to _ via
into Glu via glucose-6-phosphatase; free glucose released into blood stream
myocytes in skeletal and cardiac muscle lack glucose-6-phosphatase thus
cannot hydrolyze glucose-6P. uses glucose-6P to generate energy via glycolysis and TCA cycle
glycogen phosphorylase is the _ in liver cells
glucose sensor; response is immediate
if you were to infuse glucose into the blood stream what happens to enzymatic activity of phosphorylase and synthase
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
what are the characteristics of glycogen storage diseases?
- 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)
GSD 0:
-deficiency in glycogen synthase (pts cannot synthesize glycogen rely on glucose in diet)
GSD1a/Von Gierke disease:
- deficiency in glucose-6-phosphatase
- inefficient release of free glucose into the bloodstream by the liver in gluconeogenesis and glycogenolysis
GSD II/Pompe Disease
- 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
GSD III/Cori Disease
-deficiency in alpha-1,6-glucosidase (debranching enzyme)
GSD IV/Anderson Disease
- deficiency in glucosyl (4:6) transferase (branching enzyme)
- longer chains glucose fewer branches causes enlargement of liver and spleen
GSD V/McArdle Disease
deficiency in muscle glycogen phosphorylase
GSD VI/Hers Disease
- deficiency in liver glycogen phosphorylase
- prevents glycogen breakdown in liver ie enlargement
