Metabolism 05 - Glycogen Flashcards
what are the two tissues that have highest amount of glycogen?
Muscle glycogen, liver glycogen
Different roles of muscle vs liver glycogen
liver provides for body
muscle provides for muscle
What will happen if there is impaired hepatic muscle glycogen degradation on blood glucose levels?
Blood glucose levels will plummet during fasting periods
What will happen if there is impaired muscle glycogen degradation on glucose levels and on abiility to exercise
There is impaired glucose levels in the cell itself but not body wide; ability to exercise will be severely impaired
Impact of impaired liver or muscle glycogen degradation on the concentration of glycogen in that tissue?
Glycogen will build up
glycogen synthase and branching enzyme
Synthase- adds glucose in alpha 1,4 straight line units
branching - adds glucose at a branch point 1,6 linkage
Enzymes required to break down glycogen
Debranching enzyme
transferases
glycogen phosphorylase
glucose 6 phosphatase
Glycogen phosphorylase is active when (phosphorylated, unphosphoryalted)
phosphorylated
When will glycogen phosphorylase be active? What is the protein involved?
When phosphorylase kinase phosphorylates the glycogen phosphorylase
What hormone prevents glycogen phosphorylase kinase from activating glycogen phosphorylase?
insulin
When is the phosphorylase kinase active (what covalent modification is or is not present)
must be phosphorylated
activating factors for phosphorylase kinase
cyclic AMP , calcium
What proteins will make the phosphorylase kinase for glycogen phosphorylase active?
glucagon and epinephrine
Can insulin have a direct effect on the phosphoprotein phosphatase for glycogen phosphorylase?
Yes, it will activate it (allosteric effect); cAMP can deactivate it (also allosteric)
AMP effect on glycogen phosphorylase
can override the unactivated form to activate it
Glucose and ATP affect on glycogen phosphorylase
Can override the activated form to deactivate it
Glycogen synthase is active when (phosphorylated, dephosphorylated)
dephosphorylated
3 second messenger systems involved in regulation of glycogen metabolism
IP3/DAG, Ca, cAMP (also insulin –> GSK3)
Reciprocal regulation of glycogen syntahse and glycogen phosphorylase at the level of the second messenger systems and hormonal systems
Phosphorylation events are going to be reciprocal so that insulin will activate the synthase and inhibit the phosphorylase for example, and glucagon and epinephrine will have the opposite overall effect.
What will elevated glucose 6 phosphate do to glycogen synthesis?
Promote glycogen synthesis by overriding the inhibited state of glycogen synthase
What will elevated AMP do to glycogen synthesis
Inhibit glycogen synthesis / promote breakdown
Type 1 glycogen storage disease (von gierke)
Glucose 6 phosphatase deficiency, happens in liver and kidney –> enlarged glycogen and normal structure, individuals have enlarged liver, failure to thrive, severe hypoglycermia, hyperuricemia, hyperlipidemia, cognitive deficits
Type II glycogen storage disease (Pompe)
1,4 glucosidase (lysosomal) is fucked – happens to affect all organs, get massive increase in glycogen of nomal structure and end up with cardiorespiratory failure,d eath, hypotonia and cardiomegaly
Type III glycogen storage disease (Cori’s disease)
Amylo 1,6 debranching enzyme fucked, happens in muscle and liver, increased short outer glycogen appearance, this is like type I but milder
Type IV glycogen storage disease (Anderson’s disease)
Branching enzyme is fucked
Happens in liver and spleen
Glycogen is in normal quantities but has long branches
Progressive cirrhosis of the liver, liver failure cuauses death before age 2
Type V glycogen storage disease (McArdle)
Phosphorylase is fucked, happens in muscle
Glycogen is in moderate amount, but with normal structure. However there is limited ability to perform strenuous exercise, and painful muscle cramps
Type VI glycogen storage disease (Hers’ Disease)
Phosphorylase is fucked, happens in liver
Glycogen is in increased amount
this is like tpe I (enlarged liver, fialure to thrive, hypoglycemia and hyperuricemia, hyperlipidemia, cognitive deficits) but milder
Glycogen storage disease type VII
PFK1 is fucked up
happens in muscle
increased amount of glycogen
limited ability to perform strenuous exercise and painful muscle cramps
Glycogen storage disease type VIII
phosphorylase kinase is fucked, liver is location
increased amount of glycogen, normal morphology
Mild liver enlargement, mild hypoglycemia
Glycogen storage disease type 0
Glycogen synthase is fucked, happens in liver
glycogen is decreased
hypoglycemia, postprandial lactic acidemia, fasting ketosis
Glucagon and epinephrine promote homeostasis in what 6 ways?
- raise blood glucose levels
- promote hepatic gluconeogenesis
- promote hepatic glycogen degradation
- block hepatic utilization of glucose
- inhibit hepatic glycolysis
- inhibit hepatic glycogen synthesis
Glucagon and epinephrine inhibit hepatic glycolysis by affecting what enzymes
Inhibit PFK2 so you do not get F26BP – therefore this blocks PFK1 indirectly
Inhibit pyruvate kinase directly
Ribose 5 phosphate is important for what?
DNA and RNA synthesis
Pentose phosphate pathway generates what 2 important intermediates
NADPH
Ribose 5 phosphate
Rate limiting enzyme in pentose phosphate pathway
Glucose 6 phosphate dehydrogense
potential uses of NADPH
Relief of oxidative damage – glutathione uses NADH to get back to reduced state so it can handle oxidative stress
