411U5 - Glycogen Metabolism Purpose: Glycogen is a branched...

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Glycogen Metabolism • Purpose: Glycogen is a branched polymer of glucose; it is the stored form of G. The many branches each have a C#4 end at which GP and GS can act for rapid response. • Glycogen is stored after a meal for release: From liver when blood [G] is low to supply brain; OR In muscle for rapid activity.
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Main Enzymes of Glycogen Metabolism 1. Glycogen Phosphorylase (GP) : releases G as G1P : G n + Pi G n-1 + G1P (no ATP cost) • GP removes G only from C#4 ends of chains that are at least five G’s from a branch G1P equilibrates with G6P; this is not regulated G1P  G6P 2. Glycogen Synthase (GS) : adds G (as UDP–G) only to C#4 ends of chains. • a) Preliminary: G G6P  G1P ; • then: G1P + UTP PPi + UDP–G • b) GS rxn: G n + UDP–G UDP + G n +1
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Other Enzymes of Glycogen Metabolism • 1. Debranching enzyme: after GP has removed all but the last 4 G residues from a branch, this enzyme: • 1) catalyzes transfer of 3 G residues to the C#4 end of a nearby branch and • 2) catalyzes hydrolysis of the 1 6 linkage, producing G
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Other Enzymes of Glycogen Metabolism • 2. Branching Enzyme: transfers C#1 of a 7G residue segment (from a branch at least 11 G long) to the C#6 of a residue at least 4 G away.
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Regulation of GP , GS • 1. GP is designated by 2 systems a/b and m/o, which we will not use. Instead, we will refer to the enzymes as: phosporylated (P) or dephosphorylated (DP) ( GS is also P, DP). • 2. GP and GS are phosphorylated in response to glucagon (in the liver) (low blood [G]) and adrenalin (muscle) (fight/flight), activating GP for release of G and inactivating GS. • 3. GP kinase (GPK): GP + ATP ADP + GP–P. • 4. They are dephosphorylated in response to insulin inactivating GP, activating GS to store G.
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Regulatory effectors of GP, GPK GP-DP is: • 1) activated by AMP. MR: GP provides GlP G6P for ATP production in glycolysis , and in OP via PDH, TCA, ET, OP. ML: [AMP] is high when ATP use is rapid and ATP production is needed. 2) inhibited by ATP. MR in 1). ML: when [ATP] is high, GP doesn’t need to release G to produce more 3) inhibited by G6P. MR: G6P is an indirect product of GP. ML: when [G6P] is high, GP doesn’t need to make more. GP-P is inhibited by glucose. MR: G is indirect product: GlP  G6P G. ML: no need for more G when plenty is available GPK is activated by Ca 2+ . MR: GPK activates GP, which provides fuel for ATP production. ML: Ca 2+ triggers muscle contraction, ATP production is needed.
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Regulatory effectors of GS • GS-DP is activated by G6P: MR: G6P is indirect substrate: G6P  GlP UPD- G (feed forward) ML: when G6P is plentiful, it’s time to store G.
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Hormonal Regulation of Glycogen Metabolism • 1. The “hunger hormone”, glucagon is a signal to release G to blood from the liver via glycogenolysis and gluconeogenesis. Liver GP is activated, GS inhibited. • 2. Adrenalin (epinephrine) is a signal to “break down”
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This note was uploaded on 04/22/2011 for the course BIOCHEM 411 taught by Professor Thomas during the Spring '11 term at Tennessee Martin.

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411U5 - Glycogen Metabolism Purpose: Glycogen is a branched...

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