Ciclo de KrebsFosforilação 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

carbanioncarbanion

Acetyl CoA+Oxaloacetate to CitrateEnzyme: Citrate synthase 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-AconitateEnzyme: 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 IsocitrateEnzyme: 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-KetoglutarateEnzyme: 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 CoAEnzyme: 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 SuccinateEnzyme: 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 FumarateEnzyme: 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-MalatoFumarase

Malate to OxaloacetateEnzyme: 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 + NADH + 2 H+

Fosforilação Oxidativa

Go' = -nEo'   

                               

                           

O2 + 2H+ + 2 e- H2O 0.816

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

-0.197

NAD+ + 2 H+ + 2 e- NADH + H+              -0.320NADP+ + 2 H+ + 2 e- NADPH + H+         -0.320

FAD + 2 H+ + 2 e- FADH2      -0.219

                                                                        

      

                                                                                                                                         

                                                                                                                                          

                                                                                                                 

     

                                                                                                                        

             Figure 21.29 · The structures of several inhibitors of electron transport and

                                                         

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OBRIGADA !!!