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35 Cards in this Set
- Front
- Back
glycogen
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-large polymer of glucose (up to 106 gluc/molecule)
-granules of 10-40nm in cytosol of most cells -most residues in alpha-1,4-glycosidic bonds; branches made with alpha 1,6 linkages |
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major glycogen storage sites
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liver--community oriented; 10% of weight
muscle--selfish; 2% of weight |
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glycogen phosphorylase
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-key enzyme in glycogenolysis
-catalyzes sequential removal of glucose residues from non-reducing end of glycogen molecule by phosphorolysis |
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advantages of phosphorolysis over hydrolysis
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energetically: released sugar already phosphorylated
advantage for muscle: can retain charged glucose phosphate since it lacks glucose 6-phosphatase |
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structure of glycogen phosphorylase
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coenzyme=pyridoxal phosphate
binding sites can accommodate 4-5 glucose units which can be phosphorylated without dissociation at each step (processive reaction) |
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pyridoxal phosphate
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-derivative of vitamin B6
-covalently linked to a lysine residue at active site of glycogen phosphorylase by a schiff-base -serves as an acid-base catalyst--doesn't donate its phosphate |
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glycogen phosphorylase reaction
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1) PLP donates proton to "free" phosphate (in solution)
2) phosphate donates proton to glycogen 3) bond is broken to a glucose carbocation and glycogen(n-1) 4) carbocation=unstable so attacked by phosphate yielding PLP + glucose 1-P |
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phosphoglucomutase
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-converts glucose 1-P to glucose 6-P
-adds its phosphoryl group to make gluc 1,6 bp then it takes phosphoryl group on 1 |
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transferase (glycogen metabolism)
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moves 3 glucose residues from branched glycogen chain to main chain--it leaves 1 1,6-linked glucose
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debranching enzyme
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alpha 1,6 glucosidase--hydrolyzes remaining 1,6 linked residue to glucose after transferase has moved 3 to main chain
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why is branching important?
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-enhances solubility of molecule
-increases sites for degradation and synthesis |
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3 fates of glucose 6-P
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glycolysis, PPP, blood for use by other tissues
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regulation of glycogen phosphorylase
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-allosteric effectors that signal energy charge of cell
-hormones (insulin, epinephrine, glucagon) via phosphorylation |
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forms of glycogen phosphorylase
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-R (active) and T (inactive): interconverted by allosteric effectors
-a (usually active) and b (usually inactive): interconverted by phosphorylation/dephosphorylation |
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R and T state interconversion of glycogen phosphorylase
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high [AMP]-->stabilizes R state
high [ATP]--> negative allosteric effector--competes with AMP glucose 6-P also favors T state (feedback inhibition) |
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a and b interconversion of glycogen phosphorylase
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phosphorylase b--usually inactive unless high [AMP]
phosphorylase a--always active in resting muscle, almost all is in form b when exercise starts, high [AMP] activates b form and hormones will lead to phosphorylation (and thus form a) |
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a and b interconversion of glycogen phosphorylase in liver
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a is most responsive T-to-R transition
-glucose acts as negative regulator--liver exports gluc to other parts of body so fi there is gluc present from diet, no need to mobilize more -insensitive to regulation by AMP--liver doesn't undergo dramatic changes in energy charge |
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phosphorylase kinase
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-phosphorylates phosphorylase a
-requires Ca++ and phosphorylation -PKA catalyzes phosphorylation and cAMP activates PKA -can be partly activated by Ca++ (has calmodulin as subunit) which is important because muscle contraction is triggered by release of Ca++ |
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epinephrine/glucagon and glycogen synthesis
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-hormones elevate cAMP and cAMP allosterically activates PKA which phosphorylates phosphorylase kinase which phosphorylates phosphorylase a
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how does cAMP activate PKA?
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by freeing up catalytic site
regulatory subunit occupies kinase catalytic site with pseudosubstrate--released when cAMP binds |
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glucose transport into cells
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GLUT: family of glucose transporters
GLUT 1,3,4,5--> at normal glucose levels, can easily take up glucose from bloodstream GLUT 2--> in pancreas and liver--only under high glucose concentrations will it take up glucose |
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activated glucose (glucose donor)
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uridine diphosphate glucose
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reaction involving UDP
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gluc 1-P + UTP<----->UDP-gluc + PPi----> 2Pi
catalyzed by UDP-glucose pyrphosphorylase (first part, readily reversible, but hydrolysis of pyrophosphate drives rxn) |
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glycogen synthase
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-adds glycosyl units to non-reducing terminal residues of glycogen in an alpha 1,4 linkage
-can only add units to a chain > 4 residues long so needs primer (glycogenin) |
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glycogenin
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-"primer" for glycogen synthesis
-has 2 identical units--each has oligosaccharide of alpha-1,4 glucose units -is a glycosyltransferase -each subunit catalyzes addition of glucosyl to the other--initially at Tyr-OH -remains in glycogen molecule |
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branching in glycogen synthase
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involves transfer of ~7-C segment from an alpha-1,4 linkage to an alpha 1,6 linkage
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storage of glucose in glycogen requires how much energy?
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2 ATP/glucose
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how is glycogen synthase regulated?
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key regulatory enzyme
-can be regulated by phosphorylation -hormonally controlled by cAMP like glycogen phosphorylase but phosphorylation has opposite effect--decreases enzyme activity |
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protein phosphatase 1
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-inactivates phosphorylase kinase and phosphorylase a by dephosphorylating them
-decreases rate of glycogen breakdown -removes phosphoryl group from glycogen synthase b to convert it to active a form |
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reguation of protein phosphatase 1 by glucose
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-gluc activates PP1
-liver sense change in [gluc]--phosphorylase a is sensor -PP1 binds tight to phos a when in R state but is inactive when bound 1) glucose binds to and inhibits glycogen phos a in liver--forms T state 2) T state of phos a doesn't bind PP1 so dissociates and activates 3) free PP1 dephosphorylates glyc phos a and glyc. synth b--activates synthesis |
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insulin regulation of glycogen synthesis
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1) insulin stimulates protein kinases
2) protein kinases phosphorylate and inactivate glycogen synthase kinase 3) prevents continued phosphorylation of glycogen synthase so PP1 can dephosphorylate and activate it |
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epinephrine and glucagon regulation of glycogen synthesis
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inhibit PP1
-PKA phosphorylates regulatory subunit Gm releasing catalytic subunit (reduces activity) -PKA phosphorylates an inhibitor that inactivates PP1 |
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glycogenolysis
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breakdown of glycogen
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we can digest which linkages binding glucose moleculres
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alpha 1,4--not beta 1,4
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sites of glycogen storage
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liver and muscle
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