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Ciclo de Krebs
Fosforilação Oxidativa

   PROFESSORA : ADRIANNE MENDONÇA
Funções do Ciclo,

-Gerar ATP, coenzimas reduzidas
-“Gerar” intermediários para vias biossínteses
-Ciclo é estágio final de várias vias
Complexo piruvato dehidrogenase
TPP   ↓ Grupo reativo
      ↓ Grupo reativo




      ↓

      carbanion
       carbanion
Acetyl CoA+Oxaloacetate to Citrate
    Citrate synthase
Enzyme:

Reaction: Condensation
Acetyl CoA condenses with oxaloacetate first,to form citryl CoA. Then citryl CoA is
hydrolyzed to citrate and CoA.
Prosthetic group: No
Citrate to cis-Aconitate
Enzyme: Aconitase
Reaction: Dehydration
Citrate is isomerized to isocitrate by this first dehydration and yields cis-aconitate as an intermediate.
Prosthetic group: Fe-S
cis-Aconitate to Isocitrate
Enzyme: Aconitase
Reaction: Hydration
Hydration of cis-aconitate gives the interchange of H atom and OH group from the step 2.
Prosthetic group: Fe-S
Isocitrate to alpha-Ketoglutarate
Enzyme: Isocitrate dehydrogenase
Reaction: Oxidative decarboxylation
Dehydrogenation of isocitrate occurs and yields oxalosuccinate as an intermediate.Then
CO2 leaves to have alpha-ketoglutarate.This reaction gives NADH.
Prosthetic group: No
alpha-Ketoglutarate to Succinyl CoA
Enzyme: alpha-Ketoglutarate dehydrogenase complex
Reaction: Oxidative decarboxylation
This mechanism is almost as same as the reaction of the oxidative
decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase complex.
This reaction gives one NADH.
Prosthetic group: Lipoic acid, FAD, TPP
Succinyl CoA to Succinate
Enzyme: Succinyl CoA synthetase
Reaction: Substrate-level phosphorylation
The thioester bond of succinyl and CoA is an energy rich bond. Thus only this step gives a
high-energy phosphate compound,GTP from the couple reactions of the thioester bond
cleavage and the phosphorylation of GDP.
Prosthetic group:No




     GTP + ADP → GDP + ATP
Succinate to Fumarate
Enzyme: Succinate dehydrogenase
Reaction: Oxidation
The two hydrogens of succinate leave to an acceptor, FAD. Then this reaction yields fumarate and
FADH2.
Prosthetic group: FAD & Fe-S
Fumarato → l-Malato
Fumarase
Malate to Oxaloacetate
Enzyme: Malate dehydrogenase
Reaction: Oxidation
Malate is dehydrogenated to form oxaloacetate. The hydrogen acceptor is NAD. So this reaction
yields NADH.
Prosthetic group: No
1 cal~ 4 Joules
Note AcetilCoA é na prática queimado no ciclo,

Os intermediários do ciclo não são!!
Elementos necessários ao TCA, reações anapleróticas repõem intermediários do Krebs.
Repor ciclo para funcionar

Bactérias e plantas
2 Ac CoA + NAD+ + 2 H2O  Succinato + 2 CoA +
Fosforilação Oxidativa
∆Go' = -nℑ∆Eo'
Fe3+ + e- → Fe2+                                  0.771


NO3-+2 H++2 e- → NO2-+H2O
                                                  0.421


Cytochrome f( Fe3+)+ e- → cytochrome f(Fe2+)
                                                  0.365

Cytochrome a3( Fe3+)+ e- → cytochrome a3(Fe2+)    0.350
Cytochrome a(Fe3+)+ e- → cytochrome a(Fe2+)       0.290


Cytochrome c( Fe3+)+ e - → cytochrome c(Fe2+)     0.254
Cytochrome c1( Fe3+)+ e - → cytochrome c1(Fe2+)   0.220
UQH ⋅ + H1 + e- → UQH2 (UQ=coenzyme Q)            0.190
UQ + 2 H+ + 2 e- → UQH2                           0.060
Cytochrome bH(Fe3+) + e - → cytochrome bH(Fe2+)   0.050
Fumarate + 2 H+ + 2 e- → succinate                0.031
UQ + H+ + e- → UQH ⋅                              0.030
Cytochrome b5( Fe3+)+ e - → cytochrome b5(Fe2+)   0.020
[FAD]+2 H++2 e- → [FADH2]                         0.003-0.091*
Cytochrome bL( Fe3+)+ e - → cytochrome bL(Fe2+)   -0.100
Oxaloacetate + 2 H+ + 2 e- → malate               -0.166
Pyruvate + 2 H+ + 2 e- → lactate                  -0.185
FAD + 2 H+ + 2 e- → FADH2          -0.219




NAD+ + 2 H+ + 2 e- → NADH + H+     -0.320
NADP+ + 2 H+ + 2 e- → NADPH + H+   -0.320
Figure 21.29 · The structures of several inhibitors of electron transport and
F
F
OBRIGADA !!!

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Ciclo de krebs

  • 1. Ciclo de Krebs Fosforilação Oxidativa PROFESSORA : ADRIANNE MENDONÇA
  • 2. Funções do Ciclo, -Gerar ATP, coenzimas reduzidas -“Gerar” intermediários para vias biossínteses -Ciclo é estágio final de várias vias
  • 3.
  • 4.
  • 5.
  • 6.
  • 8.
  • 9. TPP ↓ Grupo reativo ↓ Grupo reativo ↓ carbanion carbanion
  • 10.
  • 11.
  • 12.
  • 13.
  • 14. Acetyl CoA+Oxaloacetate to Citrate Citrate synthase Enzyme: Reaction: Condensation Acetyl CoA condenses with oxaloacetate first,to form citryl CoA. Then citryl CoA is hydrolyzed to citrate and CoA. Prosthetic group: No
  • 15. Citrate to cis-Aconitate Enzyme: Aconitase Reaction: Dehydration Citrate is isomerized to isocitrate by this first dehydration and yields cis-aconitate as an intermediate. Prosthetic group: Fe-S
  • 16. cis-Aconitate to Isocitrate Enzyme: Aconitase Reaction: Hydration Hydration of cis-aconitate gives the interchange of H atom and OH group from the step 2. Prosthetic group: Fe-S
  • 17. Isocitrate to alpha-Ketoglutarate Enzyme: Isocitrate dehydrogenase Reaction: Oxidative decarboxylation Dehydrogenation of isocitrate occurs and yields oxalosuccinate as an intermediate.Then CO2 leaves to have alpha-ketoglutarate.This reaction gives NADH. Prosthetic group: No
  • 18. alpha-Ketoglutarate to Succinyl CoA Enzyme: alpha-Ketoglutarate dehydrogenase complex Reaction: Oxidative decarboxylation This mechanism is almost as same as the reaction of the oxidative decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase complex. This reaction gives one NADH. Prosthetic group: Lipoic acid, FAD, TPP
  • 19. Succinyl CoA to Succinate Enzyme: Succinyl CoA synthetase Reaction: Substrate-level phosphorylation The thioester bond of succinyl and CoA is an energy rich bond. Thus only this step gives a high-energy phosphate compound,GTP from the couple reactions of the thioester bond cleavage and the phosphorylation of GDP. Prosthetic group:No GTP + ADP → GDP + ATP
  • 20. Succinate to Fumarate Enzyme: Succinate dehydrogenase Reaction: Oxidation The two hydrogens of succinate leave to an acceptor, FAD. Then this reaction yields fumarate and FADH2. Prosthetic group: FAD & Fe-S
  • 22. Malate to Oxaloacetate Enzyme: Malate dehydrogenase Reaction: Oxidation Malate is dehydrogenated to form oxaloacetate. The hydrogen acceptor is NAD. So this reaction yields NADH. Prosthetic group: No
  • 23. 1 cal~ 4 Joules
  • 24. Note AcetilCoA é na prática queimado no ciclo, Os intermediários do ciclo não são!!
  • 25.
  • 26.
  • 27.
  • 28.
  • 29. Elementos necessários ao TCA, reações anapleróticas repõem intermediários do Krebs.
  • 30. Repor ciclo para funcionar
  • 31.
  • 32.
  • 33.
  • 35.
  • 36.
  • 37. 2 Ac CoA + NAD+ + 2 H2O  Succinato + 2 CoA +
  • 38.
  • 40.
  • 42.
  • 43. Fe3+ + e- → Fe2+ 0.771 NO3-+2 H++2 e- → NO2-+H2O 0.421 Cytochrome f( Fe3+)+ e- → cytochrome f(Fe2+) 0.365 Cytochrome a3( Fe3+)+ e- → cytochrome a3(Fe2+) 0.350 Cytochrome a(Fe3+)+ e- → cytochrome a(Fe2+) 0.290 Cytochrome c( Fe3+)+ e - → cytochrome c(Fe2+) 0.254 Cytochrome c1( Fe3+)+ e - → cytochrome c1(Fe2+) 0.220 UQH ⋅ + H1 + e- → UQH2 (UQ=coenzyme Q) 0.190 UQ + 2 H+ + 2 e- → UQH2 0.060 Cytochrome bH(Fe3+) + e - → cytochrome bH(Fe2+) 0.050 Fumarate + 2 H+ + 2 e- → succinate 0.031 UQ + H+ + e- → UQH ⋅ 0.030 Cytochrome b5( Fe3+)+ e - → cytochrome b5(Fe2+) 0.020 [FAD]+2 H++2 e- → [FADH2] 0.003-0.091* Cytochrome bL( Fe3+)+ e - → cytochrome bL(Fe2+) -0.100 Oxaloacetate + 2 H+ + 2 e- → malate -0.166 Pyruvate + 2 H+ + 2 e- → lactate -0.185
  • 44. FAD + 2 H+ + 2 e- → FADH2 -0.219 NAD+ + 2 H+ + 2 e- → NADH + H+ -0.320 NADP+ + 2 H+ + 2 e- → NADPH + H+ -0.320
  • 45.
  • 46.
  • 47.
  • 48.
  • 49.
  • 50. Figure 21.29 · The structures of several inhibitors of electron transport and
  • 51.
  • 52. F
  • 53. F
  • 54.
  • 55.