Term
|
Definition
-a peptide hormone secreted by b cells of the pancreas in response to high blood glucose, has the overall effect of promoting energy storage
Cell surface receptors bind insulin; the cascade of intracellular phosphorylation that results is very different than that due to glucagon stimulation, but affects enzyme phosphorylation states-
overall effect here is dephosphorylation at PKA and other sites- decreased kinase activity as well as activation of PP1
|
|
|
Term
Insulin effects on muscle |
|
Definition
-glycogen storage are on Glc transport as well as dephosphorylation of BOTH synthase and phosphorylase |
|
|
Term
|
Definition
glycogen storage are mainly through promoting dephosphorylation of BOTH synthase and phosphorylase- Glc transport in liver is high capacity and insensitive to insulin |
|
|
Term
Hormonal Signals Regulate the Phosphorylation State |
|
Definition
•Glucagon and some other hormones,
e.g., epinephrine, act through cAMP production and PKA activation -> phosphorylation of glycogen synthase and phosphorylase
•These hormones promote glycogenolysis and inhibit glycogenesis
|
|
|
Term
Glucagon acts through cAMP |
|
Definition
Glucagon is a peptide hormone released by pancreatic a cells in response to low blood glucose (fasting, starvation, disease state)- promotes liver glucose production and release
Reminder: Frc-2,6-bisphosphate, whose production is regulated by phosphorylation, activates glycolysis
|
|
|
Term
Coordination in liver when glucose is low |
|
Definition
|
•When blood [Glc] is low, glucagon is released, resulting in increased intracellular [cAMP] in liver.
–Phosphorylation of liver PFK-2/FBPase-2, inactivating PFK-2 activity and activating FBPase-2 activity => [Frc-2,6-bisP] decreases.
–PFK activity decreases, inhibiting glycolysis.
–FBPase activity increases, stimulating gluconeogenesis, providing a second means of Glc production.
–Glc resulting from concurrent stimulation of glycogen degradation is transported out of cells.
|
|
|
Term
Coordination in liver when glucose is high |
|
Definition
•When blood [Glc] is high, intracellular [cAMP] decreases
Liver PFK-2/FBPase-2 is dephosphorylated, activating PFK-2 -> increase in [Frc-2,6-P]
•With increased [Frc-2,6-bisP], PFK is activated, FBPase is inhibited
=> net glycolytic flux changes from gluconeogenesis to glycolysis, concurrent with dephosphorylation promoting net glycogen synthesis
|
|
|
Term
Coordination in skeletal and heart muscle |
|
Definition
|
•Different PFK-2/FBPase-2 isozymes are present.
•The skeletal muscle isozyme lacks a cAMP-dependent phosphorylation site so is not subject to cAMP/PKA regulation- Glc abundance influences pathway activities.
•Phosphorylation of the heart enzyme activates rather than inhibits PFK-2. Thus, hormones that stimulate glycogen breakdown also increase heart muscle [Frc-2,6-bisP], stimulating glycolysis.
•Increased glycogen breakdown is coordinated with increased glycolysis.
|
|
|
Term
Epinephrine, a Tyr derivative, also promotes cAMP production |
|
Definition
Epinephrine, produced by the adrenal medulla, promotes readiness for rapid and strenuous activity (fight or flight)
Epinephrine abinds b-adrenergic receptors on liver and muscle cells (and at other tissues), promoting cAMP production, and thus, PKA activity
|
|
|
Term
Epinephrine Action on Muscle |
|
Definition
Activated PKA stimulates glycogen phosphorylase and inhibits synthase
Activated PKA also promotes glycolysis in heart muscle
|
|
|
Term
Epinephrine action on liver is through two adrenergic receptor types |
|
Definition
b-adrenergic receptor binding stimulates cAMP production and thus, PKA activity
a-adrenergic receptor binding promotes a series of events that result in cytosolic Ca2+ increase.
This maximizes glycogen phosphorylase activation and glycogen synthase inhibition.
|
|
|
Term
|
Definition
-is in the Glc-6-Phosphatase System
•One of the most severe glycogen metabolism deficiency classes, but patients managed into adulthood now
•Subdivided into Type Ia and Type Ib (at least)
•Both inherited as autosomal recessive disorders
•Enzyme activity is deficient in liver, kidney, and intestinal mucosa
|
|
|
Term
|
Definition
•Deficiency of glycogen debranching enzyme activity; autosomal recessive inheritance
•Presence in liver and/or muscle of high levels of abnormal glycogen (short outer chains)
•Less severe than Type I in most cases (highly variable)
•Can affect liver and muscle (Type IIIa) or liver alone (Type IIIb)
•Both disorders present in infancy or childhood with symptoms similar to Type I EXCEPT no lactic acidemia, no uricemia, no fatty deposits in liver
|
|
|
Term
|
Definition
-McArdle Disease; Myophosphorylase Deficiency
•Deficiency of the only phosphorylase isoform in muscle (additional isoforms expressed in other tissues)
•Inheritance is autosomal recessive
•Less severe than most glycogen storage diseases
•Patients often present in adulthood with muscle pain and weakness following exercise; additional symptoms after exercise include rhabdomyolysis, elevated blood ammonia, inosine, hypoxanthine, and uric acid
•Treatment can be to increase Glc intake before exercise (or to avoid strenuous exercise) and/or increase protein in the diet
|
|
|
Term
|
Definition
•Deficiency in glycogen phosphorylase activity- can be deficient in phosphorylase or phosphorylase kinase: 6 subtypes
•Autosomal recessive (most subtypes) or X-linked recessive
•Patients present with hepatomegaly, hypoglycemia, increased liver glycogen with normal structure
|
|
|
Term
|
Definition
Tarui Disease
•Deficiency of muscle phosphofructokinase activity- only isozyme expressed in muscle
•Autosomal recessive inheritance
•Clinical features like those of Type V except that muscle symptoms are present in childhood and are more severe, hyperuricemia occurs after exercise, and abnormal fibrillar glycogen accumulates in muscle (effect of elevated Glc-6-P levels on synthase?)
•Treatment? Avoid strenuous exercise to avoid symptoms
|
|
|
