Glycogen Metabolism Flashcards
What is the major glucose storage molecule in the human body?
Glycogen
What tissues prefer glucose as their primary source of energy? Why?
Brain: FA cannot cross the blood-brain barrier
RBCs: no mitochondria
Kidney medulla, lens/cornea of the eye, and testes: poor mitochondria
Exercising muscle: short term, high intensity exercise
What are the main sources of glucose? (3)
When are they active?
Diet (sporadic) – quickly cleared out after eating (3 hours)
Short term fasting – degradation of liver glycogen, active after diet is depleted
Long term fasting – gluconeogenesis, synthesis of glucose from non-carbohydrate molecules, active after glycogen stores deplete, synthesized in liver and kidney cortex
Describe the process between from glycogen to blood glucose during fasting
What must happen in the liver in order to be able to successfully increase blood glucose?
Glycogen –> G-1-P –> G-6-P (gluconeogenesis also goes to G-6-P) –> G-6-Phosphatase –> Glucose –> blood glucose
Liver must down regulate glucose consumption during fasting by down-regulating glycolysis
What part of the cell is glycogen stored in? What is it bound to?
It is stored in the cytoplasm. It is covalently bound to glycogenin proteins at the center
Explain the structure of glycogen
They are a branched chain polysaccharide of glucose, the linear part is linked alpha 1-4, the branches are linked alpha 1-6, branching occurs every 8-10 glucose molecule
Why is UDP-Glucose important?
What catalyzes its formation?
UDP is the nucleotide active form, monosaccharides have to be nucleotide activated to build oligo or polysaccharides
Formation of UDP-Glucose is catalyzed by UDP-glucose-phosphorylase
In what part of the cell is glycogen degraded? Which is minor and which is major? What enzyme is used?
Minor route is the lysosomes using acid alpha-glucosidase (alpha 1-4)
Major route is in the cytoplasm by glycogen phosphorylase
Once G-6-P is synthesized from glycogen, the muscles and the liver use them differently. Explain
Muscle uses G-6-P directly for glycolysis. The liver removes phosphate to make glucose for release into the circulation
Explain the process of phosphate removal from G-6-P in the liver. Include the enzymes used as well as the transporters
G-6-P will be transported from the cytoplasm to the ER by G-6-P translocase
G-6-Phosphatase removes the phosphate
GLUT-7 will transport the glucose back to the cytoplasm
GLUT-2 will transport the glucose into the circulation
Why can’t the muscle release glucose into the circulation?
It does not contain the enzyme G-6-Phosphatase, which cleaves off the phosphate from G-6-P to make free glucose
Explain the deficiency, organs involved, blood metabolites and effects of Type 0
Deficiency in glycogen synthase. No hepatomegaly. Ketotic hypoglycemia after overnight fast because diet will not be enough to maintain blood glucose levels, ketone bodies through beta oxidation will occur.
Lactic acidosis because too much glycolysis will happen, pyruvate will be converted to lactic acid
No glycogen in liver
Explain the deficiency, organs involved, blood metabolites and effects of IA Gierke disease.
How is it different from Type IB?
Deficiency: G-6-Phosphatase (translocase for 1B)
Organs effect: hepatomegaly
Blood metabolites - severe fasting hypoglycemia (accumulated G-6-P), can be converted back to glycogen, which is manifested in hepatometgaly. Accumulation of G-6-P can go to the glycolytic pathway, causing lactic acidosis
In the event of hypoglycemia, FAs are released from adipose to the liver, but energy state is high, beta-oxidation does not happen
Type IB – G-6-P translocase is the problem
Explain the deficiency, organs involved, blood metabolites and effects of III, Cori disease.
Deficiency: Debranching enzyme (muscle and liver)
Organ effect: hepatomegaly, skeletal and cardiomyopathy
Blood metabolite: ketotic hypoglycemia after overnight fast, increased lipids, elevated CK
Effets: Glycogen accumulation in liver and muscle
Explain the deficiency, organs involved, blood metabolites and effects of IV, Andersen disease
Deficiency: Branching enzyme
Organs: hepatomegaly, cirrhosis, skeletal and cardiomyopathy
Blood metabolite: normal blood glucose
Other effects: glycogen with elongated fibrillar structure, less soluble, precipitation causes cell damage
Explain the deficiency, organs involved, blood metabolites and effects of type V. McArdle disease
Deficiency: glycogen phosphorylase (skeletal muscle)
Organs: cramping of skeletal muscle after exercise
Blood metabolites: normal blood glucose, increased myoglobin (shows in urine), increased CK
Other: no increase in lactate after exercise
Explain the deficiency, organs involved, blood metabolites and effects of Type VI, Hers disease
Deficiency: glycogen phosphorylase
Organ: hepatomegaly
Blood metabolites: ketotic hypoglycemia after overnight fast, mild increase in lipids
Other: glycogen accumulation in liver
What are the effects of the following hormones for the liver and the muscle?
Glucagon – affects only the liver, promotes glycogen degradation. Does not affect the muscle because it does not produce glucose to be circulated in the blood stream
Insulin – affects both, promotes glycogen synthesis
Epinephrine – affects both, promotes glycogen degradation
Between glucagon synthase and glucagon phosphorylase, which one is active when phosphorylated? Inactive?
Glycogen synthase is INACTIVE when dephosphorylated
Glycogen phosphorylase is ACTIVE when phosphorylated
What two enzymes are activated by calmodulin? What do they do?
Calmodulin dependent protein kinase – inactivates glycogen synthase
Phosphorylase kinase – activates glycogen phosphorylase A
What is one way that muscle can get energy quickly?
Release of Ca2+ from sarcoplasmic reticulum, which binds to calmodulin and activates phosphorylase kinase
