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U-M BIOLCHEM 415 - Glycogen Synthesis
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BIOLCHEM 415 1st Edition Lecture 17Outline of Last Lecture I. Glucogen is a major source of glucose storageII. Glucogen degradation creates usable glucoseIII. Regulation can be allosteric or hormonalOutline of Current Lecture IV. Different pathways are used for the synthesis and degradation of important macromoleculesV. UTP is important in glycogen synthesis VI. Regulation is important to keep glycogen synthesis goingCurrent LectureGlycogen is an important energy source- minor energy source- readily available- can provide glucoseBody needs to have glucose reserves- daily body needs ~160g- we only eat in spurts so we need reservesGlycogen synthesis1) transport glucose into cell- GLUT : family of glucose transporters2) glucose into metabolism- via glucose 6-phosphate- 3 different pathwaysThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- glycolysis, pentose-p pathway, glycogen synthesis3) glycogen synthesis needs glucose 1-phosphate- derived from glucose 6-phosphate by phosphoglucomutase- activated by UTP4) glycogen synthase- addsglucosyl units to non-reducing terminal residues- α-1,4 linkageGlycogen branching- α 1,6 branches- creates multiple ends from which synthesis can occurGlycogen synthesis starts with protein glycogenin- protein with 2 subunits- each subunit catalyzes addition of glucosylGlycogen storage highly efficient - costs 2 ATP but ultimately yields ~ 31 ATPGlycogen synthase- regulatory enzyme (through phosphorylation which is hormonally controlled)- protein kinase A inhibits glycogen synthesis via glycogen synthase kinasePhosphatases balance effects of kinases- hydrolysis of phosphates reverse the work of kinasesProtein Phosphatase 1 (PP1)- highly regulated enzyme- for efficient glycogen degradation it must be inactivated1) hormone activates protein kinase A2) PKA phosphorylates PP1 releasing catalytic subunit3) PKA phosphorylates inhibitor that further inactivates PP1 - phosphorylase active and synthase inactiveGlucose activates liver PP1- inactivephosphorylase and active glycogen synthase1) glucose binds phosphorylase and induces R  T and dissociation2) in T state, serine P is available to PP13) PP1 dephosphorylates glycogen synthase b  aInsulin and glucose coordinate glycogen synthase activation- insulin inactivates glycogen synthase kinase, preventing a futile cycleLiver glycogen metabolism (highly responsive)- glycogen synthesis generated almost immediately after critical glucoseDiabetes Mellitus- absence insulin signaling- glucose entry limited or prevented- cells starve- excess glucagon- stimulate glycogen breakdownLimited ability for strenuous exercise- lack of glucose in muscle- V, McArdle- phosphorylase defectiveSevere Hypoglycemia- lack of glucose in system- !, Von Glerke- Glucose 6-phosphate defectiveLiver cirrhosis and death - branching enzyme deficiency- IV, AndersenDietary carbohydrates can be stored as glycogen- limited storage


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U-M BIOLCHEM 415 - Glycogen Synthesis

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