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30 Cards in this Set
- Front
- Back
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What is the polymer structure of glycogen?
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--Glycogen is a polymer of glucose.
--Arranged in alpha-1,4 glycosidic linkages and alpha-1,6 glycosidic linkages. This helps store glycogen, so it's not so bulky. 1,4--side-by-side 1,6--up-and-down --Has a "reducing" end (with free carbon 4) and "nonreducing" end. --Glycogen is stored in cytoplasm of liver, muscle in GRANULES. |
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What is the role of glycogenin in the glycogen molecule?
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--Glycogenin is a little protein in the middle of the glycogen polymer.
--The "primer" in glycogen sythesis--accepts glucose residues. --OH of the tyrosine on glucogenin is attached to carbon 1 of first glucose (uses UDP-Glucose) --Glycogenin adds several more residues to the initial glucose (that its attached to), then glycogen synthase takes over. |
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What is the word for glycogen formation?
What is the word for glycogen breakdown? |
--Glycogenesis
Glucose-->Glycogen --Glycogenolysis Glycogen-->Glucose |
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What is glycogenolysis used for?
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--Glycogen stored and broken down in liver (and muscle) to provide glucose during times where it is scarce.
Basic overview GLYCOGEN--(Glycogen phosphorylase)-->G-1-P--(Phosphoglucomutase)-->G-6-P G-6-P can be used for tons of stuff.. |
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What is fate of G-6-P released from liver, muscle, and brain glycogen?
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After glycogenolysis, G-6-P has several paths it can take..
LIVER-- G-6-P--(G-6-phosphatase)-->GLUCOSE-->RELEASE MUSCLE/BRAIN G-6-P--(glycolysis)-->PYRUVATE-->LACTATE and CO2+H20 PPP can convert G-6-P-->RIBOSE+NADPH |
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What are the steps in glycogen synthesis (glycogenesis) reaction?
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--Uses UDP-glucose to add the glucose residue to the growing chain in an alpha-1,4 linkage.
1) G-6-P--(phosphoglucomutase)-->G-1-P UDP-Glucose Phosphorylase Reaction 2) G-1-P + UTP--(UDP-glucose phosphorylase)-->UDP-GLUCOSE Glycogen Synthase Reaction 3) UDP-GLUCOSE + GLYCOGEN (n residues)--(GLYCOGEN SYNTHASE)-->GLYCOGEN (n+1 residues)+ URIDINE --UDP-glucose carries glucose residues to the chain Branching Enzyme Reaction--formation of alpha-1,6 linkages. --After chain is 11 residues long, branching enzyme breaks an alpha-1,4 bond and transfers a bunch of residues to the carbon 6 of an internal rsidue, forming an alpha-1,6 bond. Causes BRANCHING. |
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What are the steps in glycogen breakdown (glycogenolysis) reaction?
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Glycogen Phosphorylase Reaction
Glycogen (n)--(Glycogen phosphorylase)-->G-1-P + Glycogen (n-1) -->uses phosphate to break alpha-1,4 bonds in the glycogen molecule, decreasing by ONE residue each time. Debranching enzyme reaction -->Glycogen phosphorylase STOPS when it reaches glucose fourth down from a branch point due to steric hindrance--debranching enzyme takes over. -->Debranching enzyme has two activities: Transferase-->removes three glucose residues nearest to non-reducing end by breaking an internal alpha-1,4 glycosidic bon--leaves one glucose residue. Alpha-1,6 glucosidase-->breaks the alpha-1,6 glycosidic bond--releases last ("branch point") glucose residue-->leaves as free glucose. |
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What is the fate of G-1-P and glucose in liver, after glycogenolysis?
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G-1-P--(phosphoglucomutase)-->G-6-P--(G-6-phosphatase)-->Glucose
Can release glucose to other cells during a fast |
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What is the fate of G-1-P and glucose in muscle, after glycogenolysis?
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G-1-P--(phosphoglucomutase)-->G-6-P
-->Muscle has no G-6-phosphatase, so it can only break G-1-P down into G-6-P |
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How do glucagon/epinephrine regulate glycogenolysis in the liver?
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Glucagon/Epinephrine are active during FAST-->want to release glucose from liver.
--Want to STIMULATE GLYCOGENOLYSIS and INHIBIT GLYCOGEN SYNTHESIS. Bind to receptor-->activate Gas-->activate adenylate cyclase-->increase cAMP-->activates PKA-->wants to PHOSPHORYLATE. Activates..glycogenolysis. Inhibits...glycogenesis, glycolysis (by phosphorylating PFK-2) |
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How do glucagon/epinephrine regulate glycogenolysis in the muscle?
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NO GLUCAGON RECEPTORS IN THE MUSCLE!
--Epinephrine wants to STIMULATE glycogenolysis, glycolysis and INHIBIT glycogenesis. Binds to receptor like always-->activates PKA-->wants to PHOSPHORYLATE things. Similar to liver--only difference: phosphorylation of PFK-2 ACTIVATES it-->get INCREASED GLYCOLYSIS. |
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How does insulin regulate glycogenolysis in the liver/muscle?
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--Stimulates liver and muscle glycogenesis and inhibits glycogenolysis.
--Stimulates cascade that DEPHOSPHORYLATES things. --Also, increases GLUT-4 transporters in muscle-->increase glucose uptake. |
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How do Glucagon/Epinephrine regulate glycogen phosphorylase?
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Glucagon/Epinephrine are active during a fast, so they want to STIMULATE glycogenolysis and INHIBIT glycogen synthesis.
-->Glycogen phosphorylase CATALYZES GLYCOGENOLYSIS--so, they want to turn it on. -->Glycogen phosphorylase is ACTIVATED by a phosphorylase kinase and INHIBITED by phosphoprotein phosphatase. -->In BOTH glycogen phosphorylase AND phosphorylase kinase, the active form is A (PHOSPHORYLATED) and the inactive form is B (DEPHOSPHORYLATED) -->The phosphoprotein phosphatase is INHIBITED by cAMP and ACTIVATED by insulin. --Glucagon and epinephrine love to PHOSPHORYLATE things, so it's easy for them to ACTIVATE this enzyme and STIMULATE glycogenolysis. --Also, their pathway generates cAMP, which INHIBITS phosphoprotein phosphatase, so ACTIVE phosphorylase can be made. So... Glucagon/Epinephrine bind to receptor-->elicit pathway that generates cAMP-->activates protein kinase A (PKA) cAMP-->INHIBITS phosphoprotein phosphatase (phosphorylase A can be made) PKA-->phosphorylates KINASE (B-->A) which phosphorylates PHOSPHORYLASE (B-->A) -->ALSO inhibits phosphoprotein phosphatase BOTH of these steps will help Glycogenolysis happen! |
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How does insulin regulate glycogen phosphorylase?
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Remember--
Glycogen phosphorylase is converted to active form by a kinase. BOTH forms are ACTIVATED by PHOSPHORYLATION (B form-->A form). Phosphoprotein phosphatase REMOVES phosphate from phosphorylase, making it inactive. This enzyme is ACTIVATED by insulin. --Insulin loves to DEPHOSPHORYLATE things, so this is also a perfect scenario. So... Insulin binds to its receptor and ACTIVATES phosphoprotein phosphatase. phosphoprotein phosphatase--> DEPHOSPHORYLATE KINASE (A-->B)-->can no longer phosphorylate phosphorylase-->no more glycogenolysis! |
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Overall, what are the activators/inhibitors of glycogen phosphorylase kinase?
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ACTIVATED (B-->A) by...Calcium, PHOSPHORYLATION by protein kinase A
INHIBITED (A-->B) by..DEPHOSPHORYLATION by phosphoprotein kinase. During muscle contraction, calcium will activate whatever it can..this leads to a better chance of obtaining energy. |
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Overall, what are the activators/inhibitors of phosphoprotein phosphatase?
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ACTIVATED by..Insulin
INHIBITED by...cAMP |
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Overall, what are the activators/inhibitors of glycogen phosphorylase?
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ACTIVATED (B-->A) by..AMP, PHOSPHORYLATION by phosphorylase kinase.
INHIBITED (A-->B) by...Glucose, ATP, DEPHOSPHORYLATION by phosphoprotein phosphatase. |
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What are the hormone regulators of glycogenolysis?
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1) Glucagon-->increase cAMP-->activates protein kinase A-->phosphorylates kinase (B-->A)-->phosphorylates phosphorylase (B-->A)-->glycogenolysis!
**Protein kinase A also inhibits phosphoprotein phosphatase, which keeps phosphorylase active. 2) Epinephrine--same. 3) Insulin--activates phosphatase-->inhibits kinase AND phosphorylase. |
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What are the allosteric controls on glycogenolysis?
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1) Calcium-->activates phosphorylase kinase.
2) AMP-->activates glycogen phosphorylase. 3) Glucose-->inhibits glycogen phosphorylase. |
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How do glucagon/epinephrine regulate glycogen synthase?
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-Glucagon/Epinephrine are high during a FAST, so want to INHIBIT glycogen synthase.
--Glycogen synthase is opposite of glycogen phosphorylase. Active form-->DEPHOSPHORYLATED (A) Inactive form-->PHOSPHORYLATED (B) So..glucagon/epinephrine begin the phosphorylation extravaganza.. Bind-->increase cAMP-->activate PKA-->activates PHOSPHORYLASE KINASE-->PHOSPHORYLATES glycogen synthase-->INHIBITS glycogen synthase-->stops glycogenesis. Also, there is a protein phosphatase present--want to keep synthase phosphorylated, so phosphatase is INHIBITED by cAMP. |
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How does insulin regulate glycogen synthase?
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--Insulin wants to ACTIVATE glycogen synthesis.
--Binds to receptor-->INHIBITS glycogen synthase kinase-->can not phosphorylate glycogen synthase-->keeps it active! --Also, phosphatase is ACTIVATED by insulin-->so, it will DEPHOSPHORYLATE the synthase, so it is ACTIVE and can allow glycogenesis. |
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What are hormone regulators of glycogenesis?
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1) Glucagon-->increase PHOSPHORYLATION of GLYCOGEN SYNTHASE (inhibits it) and inhibits phosphatase
2) Epinephrine--same. 3) Insulin--ACTIVATES phosphatase and INHIBITS glycogen synthase kinase (GSK) |
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What are allosteric regulators of glycogenesis?
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1) Calcium activates calmodulin kinase-->phosphorylates glycogen synthase-->INHIBITS it.
2) G-6-P can ACTIVATE glycogen synthase, directly. |
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How does insulin/glucagon/epinephrine inhibit phospoprotein phosphatase?
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-->Phosphoprotein Phosphatase is phosphatase present in both glycogenolysis and glycogen synthesis--tries to de-phosphorylate glycogen synthase and glycogen phosphorylase
Gluca/Epi--PKA phosphorylates a glycogen regulatory protein (G)-->causes phosphatase to dissociate from G and lose activity. -->PKA also phosphorylates the inhibitor protein (I), which binds and FULLY inactivates phosphatase. Insulin-- Stimulates dephosphorylation of G-->phosphatase re-joins with G-->active enzyme! |
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How does glucose allosterically activate glycogen synthesis?
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--Allows liver to shut off glycogenolysis quickly, once new glucose is introduced.
--Liver contains Glut 2, which has high Km-->glucose enters liver cells-->binds to glycogen phosphorylase and inhibits it (converts it to B form)--also makes it a better substrate for phosphatase. --phosphorylase B does not inhibit phosphatase (like A) and allows phosphatase to dephosphorylate and activate the glycogen synthase. --Only a temporary fix--need insulin to maintain this inhibition. |
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What is type I glycogen storage disease?
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--Von gierke disease.
--No G-6-phosphatase or transport system. --Affects liver and kidney. --High glycogen. Sx's--hypoglycemia (liver/kidney can't release glucose), hyperlipemia and ketosis (B-oxidation is increased), high pyruvate/lactate (tons of G-6-P-->tons of glycolysis) |
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What is type II glycogen storage disease?
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--Pompe disease
--Defect in lysosomal enzyme --Affects all organs. --Glycogen gets into lysosomes-->is not degraded-->lysosomes ENGORGED with glyogen-->toxicity. Sx's--cardiorespiratory failure, death. |
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What is type III glycogen storage disease?
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--Cori disease
--Defect in debranching enzyme (glucosidase) --Affects muscle, liver --Glycogen can't be broken down completely--get tons of short, little, half-digested glycogens in the system. |
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What is type IV glycogen storage disease?
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--Andersen disease
--Defect in branching enzyme. --Affects liver, spleen. --Can't make glycogen correctly-->generate huge glycogen chains w/no branches-->can build up in the liver-->cause cirrhosis. |
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What is type V glycogen storage disease?
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--McArdle disease.
--defect in phosphorylase. --affects muscle. --Initial exercise is inhibited, because you are not generating ATP efficiently (crappy glycogenolysis). --However, get a "second wind" when blood-borne glucose and FA can supply ATP. |
