Chapt. 22 Glycolysis

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Chapt. 22 Glycolysis. Ch. 22 Glycolysis Student Learning Outcomes : Explain how glucose is universal fuel, oxidized in every tissue to form ATP Describe the major steps of glycolysis Explain decision point for pyruvate utilization depending on oxygen Describe major enzymes regulated - PowerPoint PPT Presentation

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  • Chapt. 22 GlycolysisCh. 22 GlycolysisStudent Learning Outcomes: Explain how glucose is universal fuel, oxidized in every tissue to form ATP Describe the major steps of glycolysis

    Explain decision point for pyruvate utilization depending on oxygen Describe major enzymes regulated

    Explain lactic acidemia and causes

  • Glycolysis overviewFig. 1*Overview of Glycolysis, TCA cycle, electron transport chain:Starts 1 glucose phosphorylated2 ATP to start process Oxidation to 2 pyruvates yields 2 NADH, 4 ATPAerobic conditions: pyruvate to TCA cycle, complete oxidationNADH from cytoplasm into mitochondria to ETC (waste some)Complete oxidation total 30-32 ATP

  • Anaerobic glycolysisFig. 2In absence of oxygen, anaerobic glycolysis:Recycles NADH to permit glycolysis continueReduces pyruvate to lactateOnly 2 ATP per glucoseMay cause lactic acidemia

  • Glycolysis phasesFig. 3Glycolysis phases:Preparation: Glucose phosphorylatedCleaved to 2 triose phosphatesCosts 2 ATPATP-generating phase:Triose phosphates oxidized moreProduces 2 NADHProduces 4 ATP

  • Glycolysis step 1Fig. 41. Glucose is phosphorylated by Hexokinase with ATP:Commitment stepG6-P not cross plasma membraneIrreversible Many pathway choicesGlycogen synthesis needs G1-P

    Many tissue-specific isozymes of hexokinases

  • Glycolysis phase IFig. 5 top2 ATP convert Glucose to Fructose 1,6 bis-P;Fructose 1,6-bis-P split to 2 triosesGlyceraldehyde 3-P (and DHAP isomerized)

    Key enzymes:Hexokinase

    PFK-1 Commits to glycolysisRegulated step

  • Glycolysis phase IIFig. 5 lowerOxidation, substrate level phosphorylation yield2 NADH, 4 ATP from 1 Glyceraldehyde 3-P

    Key enzymes:Glyceraldehyde 3-P dehydrogenaseHigh-energy bond

    Pyruvate kinase:Regulated step

  • **Alternatie fates of pyruvateFate of pyruvate depends on availability of oxygen:Much more ATP from complete oxidation of glucoseAerobic: shuttles carry NADH into mitochondria; pyruvate can be oxidized to Acetyl CoA and enter TCAAnaerobic: pyruvate reduced by NADH to lactate, NAD+, H+Fig. 6*

  • Aerobic: Glycerol 3-P shuttle carries NADHAerobic: Glycerol 3-P shuttle carries e- from NADH into mitochondrion; regenerates cytosol NAD+Glycerol 3-P diffuses across outer memberane, donates e- to inner membrane FAD enzymeLoses some energy FAD(2H) not NADH

    Fig. 7Bacteria not need shuttle since only 1 compartmentFig. 5 top

  • Anaerobic: Anaerobic glycolysis: NADH reduces pyruvate to lactate, regenerates NAD+ to continue glycolysis1 glucose + 2 ADP + 2 Pi -> 2 lactate + 2 ATP + 2 H2O + 2 H+Lactate and H+ transported to blood; can have lactic acidosisRed blood cell, muscle, eye, other tissuesTo maintain cell:Run fasterMore enzymesUse lot glucose

    Fig. 9

  • Fate of lactateFig. 10Fate of lactate:Used to make glucose (liver) Cori cycleReoxidized to pyruvate (liver, heart, skeletal muscle)lactate + NAD+ -> pyruvate + NADHLactate dehydrogenase (LDH) favors lactate, but if NADH used in ETC (or gluconeogenesis), then other directionHeart can use lactate -> pyruvate for energyIsoforms of LDH: M4 muscle; H4 heart; mixed others)

  • II. Other functions of glycolysisGlycolysis generates precursors for other paths:5-C sugars for NTPsAmino acidsFatty acids, glycerol

    Liver is major site of biosynthesisFig. 11

  • III. Glycolysis is regulatedGlycolysis is regulated by need for ATP:HexokinaseTissue specific isoformsInhibited by G-6-P Except for liverPFK-1Pyruvate kinasePyruvate dehydrogenase(PDH or PDC)Fig. 12

  • Levels of ATP, ADP, AMPFig. 13Levels of AMP in cytosol good indicator of rate ATP utilization2 ADP AMP + ATP reaction of adenylate kinaseHydrolysis ATP -> ADP increases ADP, AMPATP present highest conc:Small dec ATP -> large AMP

  • Regulation of PFK-1Regulation of PFK-1:Rate-limiting step, tetramer6 binding sites:2 substrates: ATP, Fructose 6-P4 allosteric: inhibit ATPActivate by AMPActivate by fructose 2,6 bis-P (product when excess glucose in blood)

    Fig. 14

  • Regulation of glycolysis enzymesRegulation of pyruvate kinase:R form (RBC), L (liver); M1/M2 muscle, othersLiver enz allosteric inhibition by compound in fasting; also inhibited by PO4 from Protein Kinase A Regulation of PDH (PDC):By PO4 to inactivateRate of ATP utilizationNADH/NAD+ ratioFig. 12

  • Lactic AcidemiaFig. 15Lactic acidosis:Excess lactic acid in blood > 5mMpH < 7.2From increasedNADH/NAD+

    Many causes ->Excess alcoholHypoxia

  • Key concepts Glycolysis is universal pathway by which glucose is oxidized and cleaved to pyruvate Enzymes are in cytosol Generates 2 molecules of ATP (substrate-level phosphorylation) and 2 NADH Pyruvate can enter mitochondria for complete oxidation to CO2 in TCA + electron transport chain Anaerobic glycolysis reduces pyruvate to lactate, and recycles (wastes) NADH -> NAD+

    Key enzymes of glycolysis are regulated: hexokinase, PFK-1, pyruvate kinase, PDH C

  • Review questionWhich of the following statements correctly describes an aspect of glycolysis?ATP is formed by oxidative phosphorylationTwo molecules of ATP are used in the beginning of the pathwayPyruvate kinase is the rate-limiting enzymeOne molecule of pyruvate and 3 olecules of CO2 are formed from the oxidation of 1 glucoseThe reactions take place in the matrix of the mitochondria

  • Glyceraldehyde 3-P dehydrogenaseFig. 17Glyceraldehyde 3-P dehydrogenase uses covalent linkage of substrate to S of cys to form ~P:Covalent link to S of Cys; NAD+ nearbyOxidation forms NADH + H+; ~S bondNADH leaves, new NAD+Pi attacks thioesterEnzyme reforemd

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