Krebs cycle (TCA Cycle) : Definition, pathway

Krebs cycle (Tricarboxylic Acid Cycle = TCA Cycle)

The steps of this cycle were given by Hans Krebs in 1931. Acetyl-CoA enters into Krebs cycle. Various steps of the cycle take place in mitochondria. As a result of different reactions taking place in a cyclic manner complete oxidation of Acetyl-CoA takes place. A number of krebs cycle intermediates are used in various anabolic pathways.

(1) The 2-carbon acetyl CoA is added to a 4-carbon oxalo acetic acid to form a 6 carbon citric acid in presence of a "condensing enzyme" citrate synthetase. The reaction utilizes one molecule of H2O and releases coenzyme A.

(2) By dehydration of citric acid is form cis-aconitic acid in presence of enzyme aconitase.

                     Aconitase

 Citric acid        →      Cis-aconitic acid + H2O

(3) By hydration of cis-aconitic acid is formed isocitric acid in presence of enzyme aconitase.
                              Aconitase
Cis-aconitic acid + H2O     →    Isocitric acid

(4) Hydrogen atoms from Isocitric acid react with NAD to form NAD.2H forming oxalo succinic acid.

                        Isocitric dehydrogenase
isocitric acid + NAD           →        Oxalosuccinic acid + NAD.2H

(5) The 6-carbon oxalosuccinic acid is decarboxylated to 5-carbon, a-ketoglutaric acid in presence of enzyme oxalosuccinic decarboxylase. One molecule of CO₂ is released in the reaction.

              Oxalosuccinic acid  →  α-ketoglutaric acid + CO₂

(6) The 5-carbon, α-ketoglutaric acid is oxidatively decarboxylated to form a 4 carbon succinyl coenzyme-A, in presence of enzyme α-ketoglutaric dehydrogenase. One molecule of Co-A is used up. One molecule of CO2 is released and the coenzyme NAD+ is reduced to NADH + H+ in the reaction.

  α-Ketoglutaric acid + NAD + CoA.SH → Succinyl-Co-A + CO₂+ NAD.2H

(7) Succinyl-Co-A is hydrolysed to form succinic acid in presence of enzyme succinic thiokinase. One molecule of H2O is used up and Co-A is released. One molecule of GDP (guanosine diphosphate) is converted to GTP (guanosine triphosphate) in the reaction. The process is termed substrate phosphorylation. The GTP can react with ADP to form ATP + GDP.

      Succinyl-Co-A + GDP+ H3PO4  →  Succinic acid + GTP + CoA-SH

(8) Succinic acid is oxidized to form fumaric acid in presence of enzyme succinic dehydrogenase. The coenzyme-FAD is reduced to FADH2 in the reaction.

          Succinic acid + FAD → Fumaric acid + FAD.2H

(9) One molecule of H2O is added to fumaric acid to form malic acid. The reaction is catalysed by enzyrne-fumarase.

             Fumaric acid + H₂O → Malic acid

(10) Malic acid is oxidized to form oxaloacetic acid in presence of enzyme malic dehydrogenose one molecule of NAD is reduced to NADH + H in the reaction.

   Malic acid + NAD → Oxaloacetic acid + NAD.2H

• Aerobic and Anaerobic Respiration: Definition, Mechanism