glycogen Flashcards
Energy sources during exercise over time
1) ATP + creatine phosphate
2) anaerobic glycolysis of muscle glycogen
3) Anaerobic oxidation of muscle glycopgen, liver glycogen, plasma glucose
4) Aerobic oxisation of plasma FFA and plasma tissue triglycerides.
Enzymes needed for glycogen synthesis
glycogen synthase: adds glucosyl units in an alpha 1,4 linkage
Branching enzymes ads glucosyl units in an alpha 1,6 linkage
Enymes required for glycogen degradation
glycogen phosphorylase- removed glucosyl units from alpha 1,4 linkage
debranching enzyme- transferase and alpha 1,6-glucosidase
Phosphorylase a regulators
Phosphorylase a is the phosphorylated and active form that causes degradation of glycogen.
activators: cAMP, PI, Ca2+. cause activation of PKA which P and activates phos a. glucagon
inhibitors: insulin, ATP
when glucose and ATP levels are high (necrosis, inflammation, liver injury) tney can bind directly to the phosphorylated form and inactivate it.
phosphorylase b regulators
inactive form that promotes glycogen synthesis. it is dephosphorylated
Activators: insulin
inhibitors: cAMP
AMP can bind directly to the b enzyme, causing a conformational change an activate from b to a form. regardless of phosphorylation status
glycogen synthase a
this is the active dephosphorylated form. glyccogen synthesis
promotors: insulin
inhibitors: cAMP
glycogen synthase b
this is the inactive phosphorylated form. no glycogen formation.
promotors: cAMP, PKA, calmodulin dependent protein kinase, PKC, caesin kinase, glucose-6-phosphate, glucagon
inhibitors: glycogen synthase kinase 3, insulin
under certain circumstances like pathological GSD, when glucose-6-P is high it directly binds to the b forms causing a conformational change to activate it.
Fasted state phophorylase and synthase
Phosphorylase a: P, active, glucagon, relaxed, glycogen degradation, high affinity to glycogen. inhibited by high glucose and ATP
Synthase b: P, inactive, glucagon, tight, substrate is UDP glucose, low affinity to substrate. inhibited by G-6-P which promotes synthesis of glycogen.
Fed state phosphorylase and synthase
Phosphorylase b: dephosphorylated, inactive form. low affinity to substrate, won’t degrade glycogen. promoted by insulin. inativated during high energy levels. when energy levels drop, have high AMP, activated form promoted for glycogen degradation.
Synthase a: dephosphorylated, active form. promotes glyocogen synthesis. promoted by insulin.
Effects of cAMP in liver
1) promotes glycogen degradation
2) inhibits glycolysis
3) inhibits glycogen synthesis
all promoted by glucagon
Effects of cAMP in heart and muscle
only activated by epi not glucagon
1) promotes glycogen degradation
2) Activates glycolysis
3) inhibits glycogen synthesis
PI in the liver
Epi activates this pathway
1) IP3 increases calcium
2) Ca2+ activates a Ca2+ depdendent PK
3) DAG activates PKC
stimulation of glycogenolysis by alpha agonists. inhibition of glycogen formation
Ca2+ in the muscle
pathway activated by nerve impulses on an AcH receptor, causes depolarization and release of Ca+.
Ca 2+ causes glycogen degradation. forma lactate
insulin in muscle cells
activates kinase mediated signaling cascade. causes uptake of glucose by GLUT 4. Promoted glycogen formation and inhibits glycolysis
Insuline in liver cells
kinase mediated signaling causes uptake of glucose. promotes glycogen formation and inhibits glycolysis.
defective glycogen synthase
affects liver
decreased glycogen
cause hypoglycemia, post prandial lactic aceidemia, and fasting ketosis.
Type I: Von Gierke disease
Glucose-6-phosphatase deficiency (translocase or enzyme).
affects the liver and kidney
increased normal glycogen
causes enlarged liver, failure to thrive, severe hypoglycemia, hyperuricemia, gouty arthiritis, hyperlipidemia (high fasting levels of fatty acid in the blood), mental retardation, lactic acidosis
Type II: Pompe Disease
defective 1,4 glucosidase (lysosomal acid maltase)
affects all organs
Massive in crease in normal structure glycogen
causes cardiorespiratory failure, death usually before age 2
Type III: Cori disease
defective glycogen debranaching enzyme
affects muscle and liver.
increased short outer glycogen
like vongierke but milder.
Type IV: Anderson’s disease
defective glycogen branching enzyme.
affects the liver and the spleen
Decreased normal amount of glycogen with long branches.
Progressive cirrhosis of liver. Liver failure causes death before age 2.
Type V: McArdler disease
defective phosphorylase.
effects muscle
moderate amount of normal structure
limited ability to perform strenous exercise, painful muscle cramps
Type VI: Hers disease
deficient phosphorylase
affects the liver
increased amount of glycogen
Like Type 1 but milder
Type VII: Tarui disease
deficient PFK-1
affects the liver
increased amount of glycogen
Like V
Type VIII
Deficient phosphorylase b kinase
affects the liver
increased amount of normal structure glycogen
mild liver enlargement and mild hypoglycemia
How does glucagon and epi inhibit glycolysis?
inhibits PFK-2 which leads to decreased F2,6BP, which leads to decreaes activity of PFK-1
Inhibits pyruvate kinase
How does glucagon and epi activate gluconeogenesis in liver
Inhibits PFK-2 which decreases F26BP which increases activity of F16BP
inhibits PK which inhibits glycolysis and promotes gluconeogenesis
How does glucagon inhibit glycogen synthesis
inhibits glycogen synthase
How does glucagon activate glycogenolysis
activates glycogen phosphorylase
activates phosphorylase kinase
How do glucagon and epi promote glucose homeostasis
raise BGL
promote hepatic glucneo
promote hepatic glycogen degradation
block hepatic utilization of glucose
inhibit hepatic glycolysis
inhibit hepatic glycogen synthesis
What are the end products of pentose phosphate pathway and what can the be used for
Used in red blood cells
NADPH- lipid biosynthesis
Ribose-5-phosphate- used in synthesis of DNA, RNAm CoA, ATP, etc
intermediates can be further metabolized by glycolysis.
What is the rate limiting enzyme in the pentose phosphate pathway?
Glucose-6-phosphate dehydrogenase
What occurs in people who have a deficiency in the glucose-6-phosphate dehydrogenase enzyme?
can lead to drug induced hemolytic anemia
red blood cells cannot maintain adequate amounts of reduces NADPH, which is required to reduce glutathione and prevent oxidative damage in the red blood cell. increased reactive oxygen species and cannot detoxify H2O2
Symptoms of glucose-6-phosphate dehydrogenase deficiency
X- linked pattern of inheritance
increased billiruin
decreased hemoglobin
increased hemolytic anemia.
Intermediates of glycolysis that are generated by the pentose phosphate pathway
Glyceraldehyde-3-phosphate
Fructose-6-phosphate
Enzymes activated by cAMP-dependent phosphrylation
phosphorylase kinase
glycogen phosphorylase
enzymes inhibited by cAMP depdendent phosphorylation
glycogen synthase
pyruvate kinase
enzymes indirectly inhibited by cAMP-dependent phosphorylation
PFK-1
enzymes indirectly stimulated by cAMP-dependent phosphorylation
fructose 1,6 bisphosphatase
enzymes inhibited by phosphorylation that is not cAMP depdendent
pyruvate dehydrogenase
