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46 Cards in this Set
- Front
- Back
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What is glycogen used for?
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Storage of carbohydrates
-Glycogen=polymer, .: when its broken down, get several molec of glucose -breakdown of glycogen provides G1P faster then the blood can take up glucose |
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Why store glycogen?
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1)Need a carb store, FA can't make glucose
2) Muscle can use glycogen faster than fat 3) Fat can't be metabolized anaeobically |
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Whats the differnce between muscle and liver glycogen?
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Muscle glycogen: available for E production for muscle contraction, no/low lvl of G6P-phosphatase, .: can't release glucose into the bloodstream
Liver: Uses glycogen to maintain blood-glucose lvls btw meals. Has G6P-phosphatase activity |
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How many reducing ends does a glycogen chain have?
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Only 1 reducing end
(The OH end on C1) |
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How are glucose monomers atttached?
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C1-C4 linkages
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Where is the branch poit? What is it for?
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-C1-C6
-provides many ends for mutliple sites of synthesis/degradation |
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What are the non-reducing ends?
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-No OH at C1, but have an OH at C4
-Non-reducing ends are where the glycogen molecules start eleasing glucose monomers |
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What are the three steps of glycogen synthesis?
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1) Synthesis of UDP-glucose
2) Elongation of pre-existing glycogen chain using UDP-glucose 3) Creation of new 1,6-glucosyl branching points |
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How do you synthesize UDP-Glucose?
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UTP + G1P --> UDP-Glucose + PPi
Enz: UDP-Glucose Pyrophosphorylase (to run this rxn, must also do: H20 + PPi --> 2Pi, to make the overall rx exergonic) |
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How is the pre-existing glycogen chain elongated?
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Can only elongate a pre-existing C1-C4 glycogen chain
.: need Glycogenin (enz that initiates the formationof a glycogen primer) -Glucose attaches to glycogenin, which attaches a couple of UDP-glucose to it -Glycogen synthase: elongates the chain, adds UDP-glucose to the non-reducing ends, forms a-1,4-glycosidic linkages -every time G1P-> glycogen -> G1P, you hydrolyze 1 UTP overall rxn: UDP-G + Glycogen (n) --> UDP + Glycogen (n+1) |
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What is the nucleoside diphosphatase kinase for?
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UDP + ATP <--> UTP + ADP
maintains [UTP] to be used for glycogen synthesis |
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How are 1,6-glucosyl branch points created?
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use Amylo-(1,4->1,6) Transglycosylase: Branching enzyme
-break a 1,4 bond to form a 1,6 bond -Transfer terminal chaon segment with 7 glucosyl residues to the C6-OH chain -each transfer segment must come from a chain of at least 11 residues -the new branch point has to be at least 4 rsidues away from the other branch points -This optimizes glycogen breakdown for fast E delivery |
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What are the 3 steps to degrading glycogen?
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1) Generating G1P
2) Debranching 3) Coversion of G1P to G6P |
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How to you regenerate G1P from glycogen?
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-Use glycogen phophorylase
-only releases glucose monomers that are at least 5 units away from a branch -highly regulated: exists in 2 fomrs: Glycogen Phosphorylase A (P form) and Glycogen Phosphorylase B (un-P form) -as a neg. dG Glycogen (n) + Pi --> Glycgen(n-1) + G1P |
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How is the glycogen molecule debranched?
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-Break a 1,4 link to make another 1,4 link
-a(1,4) glycosyl transferase: transfers an a(1,4) linked trisaccharide to nonreducing end of another branch (make new a(1,4) link) -these 3 units can be subjected to Glycogen phosphorylase (now that they're at least 5 units from a branch point) -a(1,6) glucosidase: rest of the glucosyl residue is hydrolyzed and you get Glucose and debranched glycogen (92% of glycogen's glucose is in the form of G1P and 8% remains glucose) |
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How do you convert G1P to G6P?
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-Use Phosphoglucomutase
-Needs a P tobe fully active G1P<->G1,6P<-> G6P -In muscle: G6P will go on to make ATP -In liver, G6P will be degraded back to glucose |
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How is glycogen storage efficient?
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Only use 2ATP to synthesize glycogen frm glucose (1ATP to ge G1P, then 1 UTP to get UDP-Glucose)
-When glycogen broken down and continues on to glycolysis, get a total of 37 ATP, since skip HK step (Save 1 ATP) .:(39-2=37) |
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What are the 2 regulatory mechanisms of glycogen metabolism?
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1)Allosteric control of glycogen phosphorylase and glycogen synthase
2) Covalent modification by cascade P |
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What is a monocyclic enzyme cascade?
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Only one enzyme is covalently modified
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What is a bicyclic enz cascade?
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Two enz are covalently modified (modifier of the target is itself modified)
-Flexibility and amplification of this system is huge |
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What is glycogen phosphorylase?
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-Generates G1P from glycogen
-Has 2 conformations: T (inactive) and R (active) |
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What happens to glycogen phosphorylase B under high ATP? Under highAMP?
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High ATP: phosp. B is in its inactive (T) form. you don't need more ATP, so don't need to break down glycogen
High AMP: Phosphorylase B in its active (R) form. A lot of AMP around, need ATP, need to break down glycogen |
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What regulates phosphorylase A?
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[Glucose]
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What happens when [glucose] is high?
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Have a loy of glucose, therefore don't need to break down any glycogen .: phosphorylase A is in its inactive (T) form
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Wht happens to glycogen phosphorylase A and B under physiologival conditions?
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Phosp. A: under physio. conditions, ususally have low levls of glucose in the the cell, .: Phosphorlylase A is ACTIVE
Phosp. B: under physio conditions, ATP lvls are high, .: don't need glucose, so glycogen phosphorylase B is INACTIVE |
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How is glycogen phosphorylase activated?
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Through phosphorylase kinase
-Phosphorylase kinase has 4subunits: alpha/B get P gamma: catalytic delta: calmodulin, gives enz Ca2+ sinsitivity |
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How does glycogen phosphorylase depend on phosphorylase kinase activity?
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-PKA P phosphorylase kinase
-Phos. kinase B is the inactive form, its only active if Ca2+ lvls are high --Phos. kinase a-P is the active form and is Ca2+ independent, .: phosphorylase kinase can be activated by PKA and Ca2+ -Phos. kinase a can then go and P glycogen phos. b to glyc. phos. a, which can tehn convert Glycogen --> G1P |
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How is PKA activated?
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Activated through cAMP
-(without cAMP, PKA is an inactive heterotetramer) when cAMP binds PKA's regulatory subunit, catalytc monmers become active and diss't -amt of PKA depends only on the [cAMP] |
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How is cAMP activated?
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-When no ormone present, G-ptn bound to GDP
-When hormone is present, G-ptn binds G-ptn receptor and this stimulates exchange of GDP for GTP -This then activates Adenylyl cyclase, which converts ATP--> cAMP -When GTP is hydrolyzed back to GDP, adenylyl cyclase is deactivated 9no more cAMP) |
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What happens when glycogen synthase is P? When glycogen phosphorylase is P?
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Glycogen synthase-P: inactive
Glycogen phosp.-P: active |
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What inhibits glycogen synthase B? What activates glycogen synthase b?
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Inhibitors: ATP, ADP, Pi
Activator: G6P (when G6P binds glyc synthase b, it de-P it so that more glycogen can be made, since high [G6P] ) |
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How is glycogen synthesis regulated in the muscles?
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High glucose:
-Insulin stimulates ptn kinase to P Gm subunit at 1 site -Inc of PP1C affinity for glycogen -PP1C more active, deP glycogen synthase and .: inc glycogen synthesis Low blood glucose: -Epinephrine stimulates Ptn Kinase to P Gm subunit at 2 sites. This dec affinity of PP1C for glycogen .: git can't deP glycogen synthase, .: no glycogen formed .: more glycogen broken down (since glycogen phosphorylase will be P and active) |
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What does phosphoprotein phosphatase 1 (PP1) do?
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It regulates all the demodifying rxn in the glycogen synthesis cascade
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How is PP1 activity inactivated?
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PKA P PP1 inhibitor, which binds PP1 and deactivates it
(PP1 is responsible for demodyfying glycogen synthase, glycogen phosphorylase and phosphorylase kinase) |
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What role does cAMP play?
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-Most upstream signal of glycogen metabolism
-controls the rate of this metabolism -leads to : INC glyc. phosphorylase activity DEC glyc synthase activity DEC deP of glycogen phosphorylase and glycogen synthase using PP1 -Key seconday messenger to DEGRADE glycogen => activates PKA which P glycogen synthase, glycogen hosphorylase and PP1 (also stimulates insulin) |
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What are the glycogen degradation signals in the liver?
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1) Glucagon: inc cAMP
2) Epinephrine: -inc cAMP (b-receptors) -inc Ca2+ (a-receptors, work thru PIP2) |
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Describe PIP2 intracellular signalling
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-Epinephrine binds the receptor and a subunit is separated from b-subunit and can activate Phospholipase C
-Phospholipase C catalyzes hydrolysis PIP2-->IP3 + DAG -IP3 stimulates release of Ca2+, which activates the calmodulin domain of phosphorylase kinase which can activate glycogen phosphorylase .: glycogen is degraded DAG activates PKC (inhibits glycogen synthase) |
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How is glucose exported into the bloodstream?
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Glucose can only be transported to the ER as G6P. .: must change G1P-->G6P. Do this through phosphoglucomutase
-G6P is transported through the T1 translocase into the ER -In ER, G6P--> Pi + glucose using the enzyme glucose-6-phosphatase -Glucose and Pi return cytosol thru T2 and T3 translocators -GLUT2 transporter then transports glucose into the blood |
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What are the four forms of glycogen phosphorylase?
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-Phos. a in T -form
-Phos. a in R form -Phos b in T form -Phos b in R form (a is more active form then b) |
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What happens to glycogen phosphorylase when [glucose] are inc?
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Glycogen phosphorylase is pushed towards its inactive T form (phosphate gps wil be accessible to PP1c)
If already have high amts of glucose, no need to degrade glycogen |
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Difference between initiator of glycogen synthesis in liver and in muscle?
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In liver, GLUCOSE is responsible for glycogen synthesis cascade (G6P and ATP responsible for muscle cascade)
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How does PP1 redulate deP rxns in the liver?
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-PP1 is controlled by G(l) (liver) subunit
-Phosphorylase a traps PP1-G(l), inactivating it so that PP1 can't deP anything -In high glucose, R phosp. a is shifted to T form, the PP1-Gl can deP it to get T form phosp. b -phosp. b has low affinity for PP1-Gl so it can go on to deP glycogen synthase which will then synthesize glycogen |
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Which kinases inactivate glycogen synthase?
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-PKA
-PKC (liver) -AMP-kinase (muscles) |
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What is Type 1 glycogen storage disease?
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Deficiency is Glucose-6-phosphatase
-without this, can't deP G6P, .; get a build up of G6P in ER of liver, activate glycogen synthase and inhibits glycogen phosphorylase get accumulation of glycogen in the LIVER |
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What is Type V glycogen storage disease?
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Glycogen Phosphorylase deficiency in muscle
-can't degrade glycogen quickly for E |
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What is type 6 glycogen storage disease?
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Liver phosphorylase deficiency
-can't breakfown glycogen to maintain blood glucose levels |
