CITRIC ACID CYCLE CLASS – B.Sc. PART-III(HONS.) BY KUNDAN PATEL GUEST FACULTY DEPARTMNET OF ZOOLOGY, B.N. COLLEGE, PATNA INTRODUCTION Citric acid cycle or Krebs cycle is a sequence of reactions occurring in mitochondria during aerobic respiration through which the Pyruvate, produced after glycolysis, is oxidised to CO2 & H2O. The energy released during the process is conserved in reduced electron carriers like NADH & FADH2 which are again oxidised during electron transport and its energy is conserved in ATP. It was identified by Hans Adolf Krebs in 1937 and hence also named as Krebs cycle. PRODUCTION OF ACETYL CO-A ● Pyruvate is oxidised to acetyl Co-A by the enzyme Pyruvate Dehydrogenase(PDH) complex which is a complex of multiple copies of each of the three enzymes - E1, E2 & E3 – located in the mitochondria of eukaryotes and in the cytosol of prokaryotes. ● This reaction involves five coenzymes – thiamine pyrophosphate(TPP), FAD, NAD, Coenzyme A and lipoate. ● E1 = Pyruvate Dehydrogenase ● E2 = Dihydrolipoyl Transacetylase ● E3 = Dihydrolipoyl Dehydrogenase PRODUCTION OF ACETYL CO-A PRODUCTION OF ACETYL CO-A REACTIONS OF KREBS CYCLE 1. Formation of Citrate:- ● Condensation of Acetyl-CoA with Oxaloacetate results in the formation of Citrate ● It is catalysed by Citrate synthase REACTIONS OF KREBS CYCLE 2. Formation of Isocitrate:- ● Citrate is reversively transformed to Isocitrate via the intermediary formation of the cis- aconitate ● It is catalysed by the enzyme Aconitase REACTIONS OF KREBS CYCLE 3. Oxidation of isocitrate to α- Ketoglutarate:- ● The enzyme Isocitrate dehydrogenase catalyses the oxidative decarboxylation of Isocitrate to form α- Ketoglutarate via an intermediate Oxalosuccinate ● NAD+ acts as electron acceptor REACTIONS OF KREBS CYCLE 4.Oxidation of α- Ketoglutarate to Succinyl-CoA:- ● The enzyme α- Ketoglutarate dehydrogenase complex catalyses the oxidative decarboxylation of α- Ketoglutarate to form Succinyl-CoA ● NAD+ acts as electron acceptor REACTIONS OF KREBS CYCLE 5. Conversion of Succinyl-CoA to Succinate:- ● This reversible reaction is catalysed by Succinyl-CoA synthetase ● GDP is phosphorylated to GTP REACTIONS OF KREBS CYCLE 6. Oxidation of Succinate to Fumarate:- ● This reversible reaction is catalysed by Succinate dehydrogenase ● FAD acts as electron acceptor and is converted to FADH2 REACTIONS OF KREBS CYCLE 7. Hydration of Fumarate to Malate: - ● This reversible reaction is catalysed by Fumarase REACTIONS OF KREBS CYCLE 8. Oxidation of Malate to Oxaloacetate:- ● This is the last reaction catalysed by Malate dehydrogenase ● NAD+ acts as electron acceptor in this reversible reaction REACTIONS OF KREBS CYCLE ENERGETICS S.NO. REACTION NO. OF ATP OR NO. OF ATP REDUCED ULTIMATELY COENZYMES FORMED DIRECTLY FORMED 1. Formation of Acetyl- 1 NADH 2.5 ATP CoA from Pyruvate 2. Oxidation of Isocitrate 1 NADH 2.5 ATP to α-Ketoglutarate 3. Oxidation of α- 1 NADH 2.5 ATP Ketoglutarate to Succinyl-CoA 4. Conversion of Succinyl- 1 GTP 1 ATP CoA to Succinate 5. Oxidation of Succinate 1 FADH2 1.5 ATP to Fumarate 6. Oxidation of Malate to 1 NADH 2.5 ATP Oxaloacetate SIGNIFICANCE OF THE CYCLE 1. The energy during the oxidations are conserved in the reduction of three NAD+ and one FAD and the production of one ATP or GTP 2. At the end of the cycle oxaloacetate is regenerated but the two carbon atoms appearing as CO2 are not the same two carbons that entered in the form of the acetyl group 3. Although this cycle directly generates only one ATP per turn, the four oxidation steps in the cycle provide a large flow of electrons into the respiratory chain via NADH and FADH2 and thus lead to the formation of a large number of ATP molecules during oxidative phosphorylation 4. It is an amphibolic pathway that plays an important role in oxidative catabolism of carbohydrates , amino acids and fatty acids on one hand and on the other provides precursors for many biosynthetic pathways CONCLUSION It can be concluded that citric acid cycle or Krebs cycle is an efficient mechanism to conserve the energy in the form of reduced electron carriers that further feed up the respiratory chain so that a cell can extract maximum of the energy hidden in its fuel substrates. Being amphibolic in nature it serves the purpose of catabolism and anabolism required in a cell. BIBLIOGRAPHY & REFERENCES ● Lehninger Principles of Biochemistry(W.H. Freeman and Co., New York) ● Biochemistry(Berg, Tymoczko & Stryer) ● Harper’s Illustrated Biochemistry(TMHCompanies Inc.) ● Biochemistry(M.C. Pant) THANK YOU.