Week 3 Flashcards
When glycogen is being made. . .
Insulin is high. Insulin activates protein phosphatase1 which dephosphorylates glycogen synthase and activates it. Then glycogen synthase adds UDP-glucse onto the non-reducing end of glycogen chain with n residues.
Before Glucose is added to the Glycogen chain. . .
Hexokinase makes glucose into glucose 6-phosphate. Then phosphoglucomutase makes glucose 6-phosphate into glucose 1-phosphate. Last, UDP glucose phosphorylase makes glucose 1-phosphate into UDP-glucose.
After 11 units of UDP-glucose have been added to glycogen. . .
branching enzyme will break a 1:4 bond about 7 glucoses in and make a 1:6 bond several units down. Both chains extend with 1:4 bonds until they are 11 units long and the process restarts.
Advantages to glycogen branching:
- increased solubility
2. more active ends (so glycogenolysis and glycogenesis can happen rapidly)
Glycogen’s function in the liver:
Serves as a glucose buffer for blood and all peripheral tissues
Glycogen’s function in the heart & skeletal muscle:
Glucose serves as a buffer for glucose 6-phosphate- glucose that can only be used within the cell
Defects in glycogen metabolism present as:
Fasting hypoglycemia (low glucose) & muscle pain during exercise
GSD 0: Causes and symptoms:
Cause: Glycogen synthase deficiency
Symptoms: Exercise intolerance, cardiac & muscle hypertrophy (increase size in cells) - failure to make glycogen at all
GSD I, Von Gierke’s disease - Causes, Treatment & Symptoms
Cause: Glucose 6-Phosphate deficiency - not a problem in glycogen synthesis or breakdown
Treatment: Avoid fasting, have frequent meals that take a long time to digest (injections of uncooked cornstarch)
Symptoms: Fasting hypoglycemia, lactic acidosis, hepatomegaly (due to glycogen accumulation in the liver - can’t export glucose from liver), hyperuricemia & hyperlipidemia (liver fails so you can’t package fat anymore)
GSD IIIa, Coris Disease - Cause, Treatment, Symptoms:
Cause: Deficiency of 1,6 glucosidase activity of debranching enzyeme
Treatment: Freq, high carb meals, avoid fasting, can’t consume many excess calorie
Symptoms: Affects liver & muscle, fasting hypoglycemia & ketoacidosis, hyperlipidemia, hepatomegaly, with elevated AST/ALT, patient will get liver, cardiac problems & muscle pain during exercise
GDS IIIb, Coris Disease: Cause, Treatment, Symptoms
Cause: deficiency of 1,6-glucosidase activity of debranching enzyme
Treatment: Freq. high carb meals, avoid fasted state, can’t consume excess calories
Symptoms: Affects only liver, fasting hypoglycemia & ketoacidosis, hyperlipidemia, hepatomegaly with elevated AST/ALT [accumulation of glycogen bc you can only break it down to the ‘stump’], can grow out of this form - distended stomach
GSD IV - Causes and Symptoms:
Cause: Deficiency in branching enzyme 4,6 transferase
Symptoms: Failure to thrive, hepatomegaly, liver failure, fatal
GSD V, McArdle’s disease - Causes, Treatment, Symptoms
Causes: Muscle glycogen phosphorylase deficiency
Treatment: Avoid exercise and try to build up tolerance
Symptoms: Late childhood onset exercise intolerance, myoglobinuria (myoglobin in urine) after exercise, fasting hypoglycemia, causes tissue damage - because the cell loses structure and shape
–Increases creatine kinase, exaggerated increase of creatine kinase and ammonia after exercise [Can’t use sugar so you degrade a.a. to meet energy needs]
Describe Glycogen synthesis (glyconeogenesis):
- Glycogen synthase (GSD 0) adds UDP glucose molecules until 11 units long
- Then 4:6 transferase (GSD IV) branches the glycogen core (adds a unit branch that glycogen synthase can then add 11 units onto)
- Glycogen synthase continues with glycogen synthesis
Describe Glycogen degradation (glycogenolysis):
- Glycogen phosphorylase (GSD 5) removes glucose units
- Then when 4 units away from branch, 4:4 transferase (debranching enzyme) removes 3 units
- Then alpha-1,6-glucosidase (GSD III) removes a branch point glucose from the chain.
- Then glycogen phosphrylase (GSD 5) continues to remove UDP glucose units/degrades glycogen
What two molecules regulate glycogen metabolism in the fasted state?
Epinephrine & glucagon
What molecule regulates glycogen metabolism in the fed state?
Insulin
What are the effects of glucagon in a liver cell while fasting?
- Glucagon causes cAMP to activate PKA
- PKA phosphorylates glycogen synthase (halts gluconeogenesis)
- PKA phosphorylates (activates) glycogen phosphorylase kinase which phosphorylates (activates) glycogen phosphorylase
- This causes glycogenolysis and glucose production.
What are the effects of epinephrine on the liver cell in the fasted state?
- Epinephrine activates PLC
- PLC activates DAG and IP3
- Then DAG activates PKC and IP3 activates Ca++ and calmodulin dependent kinase.
- PKC and Ca++/kinase phosphorylate glycogen synthase (inhibits glycogenogenesis) and activates glycogen phosphorylase kinase (active) which phosphorylates glycogen phosphorylase which causes glycogenolysis to occur (production of glucose)
How does insulin affect the liver cell in the fed state?
- Insulin activates IRS-1 which activates PI3K which activates PDK which activates PKB (Akt)
- PKB (Akt) phosphorylates protein phosphatase-1 (active) and glycogen synthase kinase-3 (inactive)
- This means that glycogen synthase is active and promoting glycogenogenesis (making glycogen)
What is the difference in metabolism between liver and sketal muscle?
- Skeletal has no glucagon receptor
- Skeletal has nerve impulse effects (Ca++ release)
- Work done in skeletal muscle –> releases AMP –> AMP-K –> glucose release
Virion
an extracellular virus waiting to encounter the next host cell
Some viruses can be segmented, meaning that they. . .
can re-assort when they are repackaged. This means that a virus can have different strains and that a particular animal can be infected with different types of flu at the same time.
Top strand of DNA=
Bottom strand of DNA=
Coding/sense strand (+) Template strand (-)
