Biochemistry: A Short Course -...
Transcript of Biochemistry: A Short Course -...
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Biochemistry: A Short CourseSecond Edition
Tymoczko • Berg • Stryer
© 2013 W. H. Freeman and Company
CHAPTER 25Glycogen Synthesis
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Chapter 25 Outline
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Glycogen degradation yields glucose 1‐phosphate.
UDP‐glucose is the monomer that is used to extend the glycogen chain in synthesis.
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Uridine diphosphate‐glucose (UDP‐glucose) is the glucose donor in glycogen synthesis.
UDP‐glucose is synthesized by UDP‐glucose pyrophosphorylase.
The reaction is subsequently rendered irreversible by the hydrolysis of pyrophosphate.
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Glycogen synthase, the key regulatory enzyme in glycogen synthesis, transfers a glucose moiety from UDP‐glucose to the C‐4 terminal residue of a glycogen chain to form an α‐1,4‐glycosidic bond.
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Glycogen synthase requires an oligosaccharide of glucose residues as primer.
The primer is synthesized by glycogenin, a dimer of two identical subunits.
Each subunit of glycogenin generated an oligosaccharide of glucose residues eight molecules long.
Glycogen synthase then extends this primer.
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Glycogen synthase can only synthesize α‐1,4‐linkages.
A branching enzyme generates branches by cleaving an α‐1,4‐linkage and taking a block of approximately seven glucoses and synthesizing an α‐1,6‐linkage.
Glycogen synthase can then extend the branched polymer.
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Glycogen synthase is usually inactive when in the phosphorylated b form, and is usually active when in the unphosphorylated a form.
The key regulatory process for glycogen synthase is the conversion of the b form in the T state to the active R state of the b form by binding glucose 6‐phosphate.
Note that phosphorylation has opposite effects on glycogen synthase than on glycogen phosphorylase.
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Only two molecules of ATP are required to incorporate dietary glucose into glycogen.
The complete oxidation of glucose derived from glycogen yields 31 molecules of ATP.
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Glycogen synthesis is inhibited by the same glucagon and epinephrine signaling pathways that stimulate glycogen breakdown.
Phosphorylation of glycogen synthase by protein kinase A to form glycogen synthase b inhibits glycogen synthesis.
Glycogen synthase kinase also phosphorylates and inhibits glycogen synthase.
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Protein phosphatase 1 (PP1) shifts glycogen metabolism from the degradation mode to the synthesis mode.
PP1 removes phosphoryl groups from glycogen synthase b, converting it into the more active a form.
PP1 also removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase, inhibiting glycogen degradation.
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Protein phosphatase 1 consists of a catalytic subunit (PP1) and two regulatory subunits.
A key regulatory subunit is the G subunit (GL in liver and GM in muscle) that binds glycogen and the PP1, localizing the enzyme with its substrates.
In muscle, phosphorylation of GM leads to dissociation of PP1 from glycogen and a decrease in the enzyme’s activity.
A second regulatory subunit, when phosphorylated, binds to and further inhibits PP1.
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Insulin stimulates glycogen synthesis by activating a signal transduction pathway that results in the phosphorylation and inactivation of glycogen synthase kinase.
PP1 subsequently dephosphorylates glycogen synthase, generating the active a form of the synthase.
Insulin also facilitates glycogen synthesis by increasing the number of glucose transporters (GLUT4) in the plasma membrane.
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Glycogen degradation in the liver is inhibited and glycogen synthesis is stimulated by high blood‐glucose levels.
The conversion of glycogen phosphorylase a from the R state to the T state by the binding of glucose results in the activation of PP1 that is associated with the phosphorylase.
PP1 converts glycogen metabolism from a degradation mode to a synthesis mode.
The lag between the decrease in degradation and the increase in synthesis is accounted for by the fact that only about 10% of phosphorylase molecules are associated with PP1.
IJ3
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슬라이드 23
IJ3 Ok to hyphenate blood-glucose in the second line?Isman, Jodi, 2012-02-28
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Diabetes is characterized by the presence of excess glucose and underutilization of the fuel.
Excess glucose is excreted in the urine.
In type 1 diabetes, insulin in not produced.
In type 2 diabetes, insulin is produced but the insulin‐signaling pathway is not responsive.
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Glycogen storage diseases result from a variety of biochemical defects in glycogen metabolism.
McCardle disease results from defective muscle glycogen phosphorylase.
Painful cramps occur when patients with McCardle exercise. NMR studies show that the cramping is correlated with high levels of ADP in muscle cells.
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