Lecture 39 Flashcards
In the liver, what molecules use negative feedback to prevent the conversion of glycogen to glucose 1-phosphate?
1) Glucose 6-phosphate
2) ATP
3) Glucose
In the liver, what molecule uses positive feedback to convert glucose 1-phosphate to glycogen?
Glucose 6-phosphate
In muscle, what molecules use negative feedback to prevent the conversion of glycogen to glucose 1-phosphate?
1) Glucose 6-phosphate
2) ATP
In muscle, what molecules use positive feedback to convert glycogen to glucose 1-phosphate?
1) Ca2+
2) AMP
In muscle, what molecule uses positive feedback to convert glucose 1-phosphate to glycogen?
Glucose 6-phosphate
What is glycogen storage disease type 1 (Von Gierke disease)?
1) Enzyme defect: Glucose-6-phosphatase
2) Glycogen structure: Normal
3) Organs involved: Liver, Kidney
4) Characteristics: Hypoglycemia, enlarged liver, lactic acidosis, ketosis, growth retardation, delayed puberty, progressive renal disease, hyperuricemia
5) Increased levels of glucose 6-phosphate activate glycogen synthase b, the normally inactive form
6) Treatment: Nocturnal gastric infusions of glucose or regular administration of uncooked cornstarch
What does glucose-6-phosphatase do?
Glucose 6-phosphatase is an enzyme that hydrolyzes glucose-6-phosphate, resulting in the creation of a phosphate group and free glucose
What is ketosis?
1) Ketone bodies are formed by ketogenesis when liver glycogen stores are depleted
2) Ketosis is a metabolic state where most of the body’s energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis where blood glucose provides most of the energy
What is glycogen storage disease type 2 (Pompe disease)?
1) Enzyme defect: alpha glucosidase (lysosomal)
2) Glycogen structure: Normal
3) Organs involved: Generalized
4) Characteristics: Enlarged heart, cardiorespiratory failure
What is glycogen storage disease type 3 (Cori disease)?
1) Enzyme Defect: Glycogen debranching enzyme
2) Glycogen structure: Short outer chains on fasting
3) Organs involved: Generalized
4) Characteristics: Englarged liver, moderate hypoglycemia, acidosis
What is glycogen storage disease type 4 (Andersen disease)?
1) Enzyme defect: Glycogen branching enzyme
2) Glycogen structure: Few branch points
3) Organs involved: Generalized
4) Characteristics: Cirrhosis, progressive liver failure
What is glycogen storage disease type 5 (McArdle disease)?
1) Enzyme defect: Muscle glycogen phosphorylase
2) Glycogen structure: Normal
3) Organs involved: Skeletal muscle
4) Characteristics: Muscle cramps on exercise
5) Similar symptoms are seen in glycogen storage disease type 7 in which there is decreased activity of phosphofructokinase activity in muscle
What is glycogen storage disease type 6 (Hers disease)?
1) Enzyme defect: Liver glycogen phosphorylase
2) Glycogen structure: Normal
3) Organs involved: Liver
4) Characteristics: Enlarged liver, moderate hypoglycemia and mild acidosis
5) A deficiency of liver glycogen phosphorylase kinase has been classified as either Type 8 or included in type 6. This condition is X-linked unlike the other glycogen storage diseases that have an autosomal recessive inheritance
Which two enzymes that either produce or break down glycogen are reciprocals of each other?
Glycogen synthase & glycogen phosphorylase
Describe the cAMP dependent glycogen synthase inactivation pathway (formation of glycogen)
1) Glucagon (liver) + Epinephrine (primarily muscle; also liver) receptors, when activated, cause Adenylyl Cyclase to convert ATP –> cAMP
2) cAMP activates cAMP-dependent protein kinase A by binding to its 2 regulatory subunits (R)
3) The catalytic subunits (C) can then phosphorylate Glycogen synthase a (active form) to produce Glycogen synthase b (inactive form)
4) Insulin can cause Glycogen synthase b to be dephosphorylated by protein phosphatase 1, reforming the active form of glycogen synthase a
Describe the cAMP dependent glycogen phosphorylase + glycogen phosphorylase kinase activation pathway (degradation of glycogen)
1) Glucagon (liver) + Epinephrine (primarily muscle; also liver) receptors, when activated, cause Adenylyl Cyclase to convert ATP –> cAMP
2) cAMP activates cAMP-dependent protein kinase A by binding to its 2 regulatory subunits (R)
3) The catalytic subunits (C) can then phosphorylate Glycogen phosphorylase kinase b (inactive form) to produce Glycogen phosphorylase kinase a (active form)
4) Insulin can cause Glycogen phosphorylase kinase a (active form) to be dephosphorylated by protein phosphatase 1, reforming the inactive form of glycogen phosphorylase kinase b
5) Glycogen phosphorylase kinase a can then phosphorylate glycogen phosphorylase b (inactive) to glycogen phosphorylase a (active)
6) Insulin can cause Glycogen phosphorylase a (active form) to be dephosphorylated by protein phosphatase 1, reforming the inactive form of glycogen phosphorylase b
7) Glycogen phosphorylase a (active) is used to degrade glycogen
What is the role of calcium in muscle with respect to glycogen degradation?
1) During muscle contraction, Ca2+ is released from the sarcoplasmic reticulum
2) The Ca2+ binds to the calmodulin subunit of phosphorylase kinase, activating it without phosphorylation
3) Phosphorylase kinase can then activate glycogen phosphorylase, causing glycogen degradation
What is the role of AMP in muscle?
In muscle under extreme conditions of anoxia and depletion of ATP, AMP activates glycogen phosphorylase b without it being phosphorylated
What are two types of Type 1 glycogen storage disease?
1) Type 1a: Von Gierke Disease (Glucose 6-phosphatase deficiency)
2) Type 1b: Glucose 6 phosphate translocase deficiency (affects the glucose-6 phosphate transporter, preventing its transport into the lumen of the ER from the cytosol)
What is a phosphatase?
A phosphatase is a hydrolase that enzyme that cleaves water to remove an inorganic phosphate group from a molecule
