BIOCHEM EXAM 4 L17

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jly518
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269870
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BIOCHEM EXAM 4 L17
Updated:
2014-04-09 01:10:10
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biochem
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Exam 4 content
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  1. Glycogen
    • storage form of glucose
    • found in skeletal muscle and liver
    • readily mobilized fuel source
    • branched, held together by a -1,4 and a - 1,6
  2. Glucose Homeostasis
    • I - immediately after meal
    • III - 4 hours post meal
    • IV - 16 hours post meal
  3. Glucose Degradation
  4. Glycogen Storage Diseases - McArdle's Disease
    • strenuous activity produces painful cramps and myoglobinuria (myoglobin in urine i.e. breaking down your muscles)
    • -->activity produces no increase in blood lactate levels
    • biochemical analysis:
    • -->high muscle glycogen - patients can make glycogen but cannot mobilize it
    • -->decreased levels of muscle glycogen phosphorylase (which breaks glycogen down)
  5. Glycogen Storage Diseases - Type O Glycogen Storage Disease
    • Morning drowsiness, fatigue, convulsions due to hypoglycemia
    • -->high levels of blood glucose and lactase after meals
    • biochemical analysis:
    • -->liver deficient in glycogen
    • -->lack of glycogen synthetase
  6. The glycogen storage diseases indicated what?
    • synthesis (anabolic) and degradative (catabolic) pathways are independent¬†
    • pathways must be coordinately regulated
  7. Glycogenolysis
    • glycogen degradation
    • 3 enzymes
    • --> glycogen phosphorylase
    • --> glycogen debranching enzyme
    • --> phosphoglucomutase
  8. Glycogen Phosphorylase
    • uses phosphate to break a bond
    • reaction: glycogen (n) + Pi --> glycogen (n-1) + glucose -1-phosphate
    • phosphorylysis: phosphate (not water) breaks glycosidic bond
    • rate determining step of glycogenolysis
    • removes only glucose with a-1,4 bonds, only within 4-5 glucose units of branch point (if too close to a branch can't access the access site)
    • requires pyrodoxial phosphate(PLP) covalently bound to enzyme (prosthetic group)
    • -- facilitates acid base catalysis
    • -- PLP derived from vitamin B6
  9. Glycogen debranching enzyme
    • one enzyme with 2 activities
    • a-1,4 transglycolase: transfer of a-1,4 trisaccharide to non-reducing end of glycogen (move the branch to the chain so phosphorylase can break it down)
    • a - 1,6: glycosidase: removes a-1,6 bound glucose at branch point, hydrolysis reaction
    • only reaction that directly makes glucose from glycogen
  10. phosphoglucomutase
    • isomerase
    • catalyzes reversible conversion of glucose-1-P to glucose-6-P
  11. glucose-6-phosphatase
    • strips phosphate so that you get glucose ready for transport
    • glucose-6-P cannot be transported out of cells, glucose can
    • also involved in gluconeogenesis
  12. Glycogenesis
    • glycogen synthesis
    • reaction: glycogen (n) +UDP-glucose --> glycogen (n+1) +UDP
    • 3 enzymes:¬†
    • -->UDP - glucose pyrophosphorylase
    • -->glycogen synthase
    • -->glycogen branching enzyme
  13. UDP - pyrophosphorylase
    • reaction: ????
    • substrate is glucose-1-P is NOT glucose
    • --same molecule released by glycogen phosphorylase
    • transfer of glucose to UDP has delta G ~ 0
    • --reaction driven by hydrolysis of PPi: PPi --> 2 Pi (delta G << 0)
    • common strategy to drive unfavorable reactions
  14. Glycogen Synthase
    • can only extend an existing glycogen chain
    • can only make a-1,4 linkages
  15. glycogen branching enzyme
    • makes a-1,6 bond
    • transfers 7 glucose unit chain to C6 hydroxyl every 8-12 glucose molecules
    • increases number of reactive ends
  16. glycogenin
    • autoglycosylating enzyme (can stick glucose on itself)
    • contains oligosaccharide on Tyr residue
    • makes primers for glycogen synthase
    • provides scaffold
    • also has synthase activity
  17. Steps to make a new glycogen molecule (5 total)
    • 1. attach glucose to glycogenin (Tyr residue)
    • 2. glycogenin complexes with glycogen synthase
    • 3. glycogenin-synthase adds up to 7 more glucose residues
    • 4. glycogen synthase takes over once chain is >= 8 residues long
    • 5. glycogenin dissociates from synthase but remains bound to reducing end of glycogen molecule
  18. Regulation of glycogen metabolism
    • challenge to controlling glycogen flux
    • allosteric regulation of rate determining step of both pathways
    • --glycogen phoshporylase
    • --glycogen synthase
  19. glycogen phosphorylase
    • dimer of identical subunits
    • --2 catalytic sites
    • --2 allosteric sites
    • two conformations
    • --T (less active) : buried active site, low substrate affinity
    • --R (more active): accesible active site, high substrate affinity
    • allosteric modulators
    • --activator: AMP
    • --inhibitor: ATP, glucose-6-P, glucose
    • AMP binds to allosteric site in T state (promotes T to R)
    • inhibitors bind allosteric site in T state (prevent T to R)

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