BIOLCHEM 415 1st Edition Lecture 16Outline of Last Lecture I.Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursorsII. Two ATP-consuming reaction in glycolysis become hydrolytic reactionsIII. Glyclysis and gluconeogenesis are tightly/reciprocally regulatedOutline of Current Lecture IV. Glucogen is a major source of glucose storageV. Glucogen degradation creates usable glucoseVI. Regulation can be allosteric or hormonalCurrent LectureSources of blood glucose differ in fed, fasting, and starving states- fed = ingested glucose- fasting = glycogenolysis- starved = gluconeogenesisGlycogen- major glucose storage form - in cell’s cytosol- advantage because readily available for cell use- large glucose polymer- compact and branched molecule- increases solubility- more terminal residues = more sites for degradation/synthesisGlycogen metabolism (release and storage of glucose)These 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.- glycogen degradation1) stepwise release2) entry into metabolism3) remodeling4) tissue specific allosteric/hormonal regulation5) intracellular (immediately available)Storage in liver and muscle- muscle- 40% of body mass- 2% muscle mass = glucogen- only meets the muscles needs and has no glucose 6-phosphatase- major allosteric regulatory signal = energy (AMP/ATP)- liver- 10% glycogen- 1-1.5 kg- maintains glucose homeostasis of organism- major allosteric regulatory signal = glucoseGlycogen phosphorylase releases glucose 1-phosphate- begins at non-reducing ends- several at a time- phosphorylsis (NOT hydrolysis)- allows immediate arrival at glucose phosphate- at expense of an ATP- mass-driven reaction- readily reversible reaction but mass drives the reaction forward- glucose 1-phosphate can’t enter metabolism directly- needs to be converted to glucose 6-phosphate- catalyzed by phosphoglucomutase with a 1,6-bisphosphate intermediateGlycogen phosphorylase can’t handle 1,6-branches- glycogen remodeling- phosphorylase cleaves α 1,4 bonds ~ 4 residues from 1,6 branching- transferase moves ~ 3 residues from branched to main chain- debranching by α 1,6 glucosidase is hydrolysis- only product is glucoseRegulation of glycogen metabolism - glycogen phosphorylase - allosteric and hormonal (phosphorylation)- allosteric - changes enzymatic activities- hormonal- adjusts metabolism to meet the body’s needs- details of regulation differ depending on the tissueGlycogen phosphorylase has several interconvertible forms- a/b depending on phosphorylation (hormonally triggered)- b is not phosphorylated and less active (exclusion of catalytic site)- R/T (allosterically triggered) - R is the active stateAllosteric regulation in liver- phospohrylase mostly present in a and R states- glucose high- less active- T state stabilized Allosteric regulation in muscle - phosphorylase mostly in b and T states- energy low = no need for glycogen breakdown- AMP promotes R stateHormonal glycogen regulation- fight/flight (energy burst to muscles)/starving (brain needs glucose)- glucagon (glucose/liver) and epinephrine (energy/muscle) stimulate glycogen breakdownPhosphorylase kinase Ca-binding and phosphorylation sites- Calmodulin- 4 binding sites for Ca- full activation needs both Ca and phosphorylation- doesn’t matter which comes first Epinephrine and Glucagon act on phosphorylase kinase- cascade of protein phosphorylation and activation of glycogen phosphorylase- just as important to stop cascadeInterplay - fasting- glucagon from pancreas to liver glucose released into blood- exercise- epinephrine liver and muscle glucose to blood and muscles lactate intoblood and liver Cellulose is much more abundant then glucose - found in plant cell walls- humans cannot break this down- so we use glucose- cows use cellulose for energy- comes at price of methane
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