扬州大学：《生物化学 Biochemistry》课程教学课件（讲稿）chapter 14 The citric acid cycle

The citric acid cycletricarboxylic acid (TCA) cycleKrebsCycle

The citric acid cycle tricarboxylic acid (TCA) cycle Krebs Cycle

The metabolism process after glycolysis under aerobic conditions: Under aerobic conditions, pyruvate from glycolysis is converted to acetyl.coenzyme A (acetyl-CoA) and oxidized to CO, in the tricarboxylic acid(TCA) cycle (also called the citric acid cycle)..TCA cycle are captured in the form of NADH and FADH2,and thesereduced coenzymes fuel the electron-transport pathway and oxidativephosphorylationto generate ATP.: Although two molecules of ATP come from glycolysis and two moredirectly out of the TCA cycle, most of the ATP arises from oxidativephosphorylation

The metabolism process after glycolysis under aerobic conditions • Under aerobic conditions, pyruvate from glycolysis is converted to acetyl￾coenzyme A (acetyl-CoA) and oxidized to CO2 in the tricarboxylic acid (TCA) cycle (also called the citric acid cycle). • TCA cycle are captured in the form of NADH and FADH2, and these reduced coenzymes fuel the electron-transport pathway and oxidative phosphorylation to generate ATP. • Although two molecules of ATP come from glycolysis and two more directly out of the TCA cycle, most of the ATP arises from oxidative phosphorylation

FIGURE 19.1 (a) Pyruvate produced in glycolysis is axidized in (b) the tricar-Glycolysis(a)boxylic acid (TCA) cycle. (c) Electrons liberated in this oxidation flow through theGlucostelectron-transport chain and drive the synthesis of ATP in oxidative phosphory-lation.In.eukaryotic cells, this overall process occurs in mitochondria.ADP+PNAD+NADHATPPyruvateNAD+NADHAcetyi-CoAOxidative(c)Electron transportphosphorylation(b)IntermembranespaceProtongradientHHI-H1154CitricMalateacidNADHcycletoghutarateNADHOADHADP+H.OATPPGTPGDP + PMitochondrialmatrix+[FADH2]H-NADH

The Citric Acid Cycle? Pyruvate from glycolysis is degraded to CO,·SomeATPisproduced·MoreNADHismade·NADHgoesontomakemoreATPinelectrontransportandoxidative phosphorylation

The Citric Acid Cycle • Pyruvate from glycolysis is degraded to CO2 • Some ATP is produced • More NADH is made • NADH goes on to make more ATP in electron transport and oxidative phosphorylation

The Citric Acid Cycle happened inmitochondrion matrix(Acetyl-CoA)MATRIXO-CondensationCH,-C-S.COACOA-SHHCH,-COO"234O=C-C00-HO-C-COO-citrateExracelulaCH,-COO-symthaseCH,-COO:Dehydration(Oxalcacetate)(Citrate)Dehydrogenation-H,OG--29:7kmoaconitasemalateCOOdehydrogenaseCH,COO-(Malate) HOCHCOOCH(cis-Aconitate)0-COO-COO:HydrationNADHfumaraseH,O54638aconitaseCOOHydratiorFADH2CHCH-COO(Fumarate)HCH-C-COONG-0.0NWmoCOOHO--COO: (Isocirate)MatrCEINN50-209kammogenas工isocitratgenatonInnerdehydrogenasemitochondralG-2.9dmmCH-COO"G33.5kamolOxidativemembranedecarbaxylasioncciwl-CoaCHketoglutaransynthotacocOdehCH-COO-inasOute(Succinate)COOcomplexchondrialCHCH,-COO-membrane-cooCOA-SHCHeoCS-CoAGOFCOA-SHGTP(t-Ketogiutarate)ADP(ATP)cO.0SubstrateOxidative(succinyl-CaA)ylation

The Citric Acid Cycle happened in mitochondrion matrix

TCA CentralityGlucose Citric acid cycle (TCA cycle; Krebs cycle) isGhycolysisa central pathwayPyruvate Multiple pathways feed into and from itCO2Amphibolic2eAcetyl CoARelates to both catabolism and anabolism Cyclic metabolic pathwayCitricacidGlycolysis; gluconeogenesis; pentosecydle2CO2ATphosphate are linearthe significance of this ?86

TCA Centrality  Citric acid cycle (TCA cycle; Krebs cycle) is a central pathway • Multiple pathways feed into and from it  Amphibolic • Relates to both catabolism and anabolism  Cyclic metabolic pathway • Glycolysis; gluconeogenesis; pentose phosphate are linear • the significance of this ?

Entry into the TCA Cycle· Pyruvate produced by glycolysis is a significant source of acetyl-CoAfortheTCAcycle.? In eukaryotic cells, glycolysis occurs in the cytoplasm, whereas theTCA cycle reactions take place in the mitochondria, pyruvate mustfirst enter the mitochondria to enter the TCA cycle.: The oxidative decarboxylation of pyruvate to acetyl-CoA is theconnecting link between glycolysis and the TCA cycle. The reactionis catalyzed by pyruvate dehydrogenase, a multienzyme complex.Pyruvate + CoA +NAD+→acetyl-CoA +CO,+ NADH

Entry into the TCA Cycle • Pyruvate produced by glycolysis is a significant source of acetyl-CoA for the TCA cycle. • In eukaryotic cells, glycolysis occurs in the cytoplasm, whereas the TCA cycle reactions take place in the mitochondria, pyruvate must first enter the mitochondria to enter the TCA cycle. • The oxidative decarboxylation of pyruvate to acetyl-CoA is the connecting link between glycolysis and the TCA cycle. The reaction is catalyzed by pyruvate dehydrogenase, a multienzyme complex

Pyruvate+CoA+NAD+→Acetyl-CoA+CO2+NADHHN—CH2CHCH2[paenta'enik]CH2adj.泛酸的Transition stepNHPantothenic Pyruvate dehydrogenase complexacid residueCHOH>OxidativedecarboxylationofpyruvateH;CCHAdenosincCH> Transfer of acetyl unit to coenzyme A (CoA)> Traffic directorto control flow of 2-C units fromglycolysis into TCAcycleCoenzyme A (CoA)(a)CoenzymeA(CoA)containsa residueofpantothenicacid(pantothenate),alsoknownasvitaminBs.Thesulfhydrylgroupisthesiteofattachmentofothergroups

Transition step  Pyruvate dehydrogenase complex  Oxidative decarboxylation of pyruvate  Transfer of acetyl unit to coenzyme A (CoA)  Traffic director to control flow of 2-C units from glycolysis into TCA cycle [pæntə‘θenɪk] adj.泛酸的

Transition stepPyruvate dehydrogenase complexComplexof3enzymesandseveralcoenzymes.Located in mitochondrion Pyruvate (glycolysis) must move from cytosol tomitochondrionONAmatrTmerrgronetermemeronsoACFopurtioncristsF,portioe

Transition step Pyruvate dehydrogenase complex • Complex of 3 enzymes and several coenzymes • Located in mitochondrion • Pyruvate (glycolysis) must move from cytosol to mitochondrion

Pyruvate dehydrogenase complex (PDC)·ThePDC is formed from multiple copies of three enzymes·pyruvatedehydrogenase(El,丙酮酸脱氢酶)dihydrolipoamideacetyltransferase（E2，二氢硫辛酰胺乙酰转移酶）·dihydrolipoamidedehydrogenase(E3，二氢硫辛酰胺脱氢酶）: It contains five different coenzymes.: The active sites of all three enzymes are not far from one another, and the product ofthe first enzyme is passed directly to the second enzyme, and so on, without diffusionof substrates and products through the solution.· Eukaryotic PDC, one of the largest-known multienzyme complexes is a 9.5-megadalton (MD) assembly organized structure

Pyruvate dehydrogenase complex (PDC) • The PDC is formed from multiple copies of three enzymes: • pyruvate dehydrogenase (E1, 丙酮酸脱氢酶) • dihydrolipoamide acetyltransferase (E2, 二氢硫辛酰胺乙酰转移酶) • dihydrolipoamide dehydrogenase (E3, 二氢硫辛酰胺脱氢酶). • It contains five different coenzymes. • The active sites of all three enzymes are not far from one another, and the product of the first enzyme is passed directly to the second enzyme, and so on, without diffusion of substrates and products through the solution. • Eukaryotic PDC, one of the largest-known multienzyme complexes is a 9.5- megadalton (MD) assembly organized structure