Tricarboxylic Acid Cycle -: Prepared by :- Mr. Ansari Altamash Shakeel Ahmad Assistant Professor Department of Pharmaceutical Chemistry Y. B. Chavan College of Pharmacy, Aurangabad, MS. India. email:- altamash263@gmail.com Mobile:- 09823967266 You tube: www.youtube/krebs cycle by Altamash Ansari Facebook: kerb's cycle by Altamash Ansari

Tricarboxylic acid cycle (TCA) Or Krebs cycle CITRIC ACID CYCLE Tricarboxylic acid cycle (TCA) Or Krebs cycle

INTRODUCTION Described by Hans Adolf Krebs in 1937 A feature of cell chemistry shared by all types of life. A complex series of reactions beginning and ending with the compound oxaloacetate. The cycle produces carbon dioxide and the energy-rich compound ATP.

INTRODUCTION Eight successive reaction steps. The six carbon citrate is formed from two carbon acetyl-CoA and four carbon oxaloacetate. Oxidation of citrate yields CO2 and regenerates oxaloacetate. The energy released is captured in the reduced coenzymes NADH and FADH2.

LOCATION The citric acid cycle enzymes are found in the matrix of the mitochondria

OVERVIEW OF KREBS CYCLE Acetyl CoA (2C) CoA Citrate (6C) α-Ketoglutarate (5C) Succinyl CoA (4C) Oxaloacetate (4C) CO2 CO2

Conversion of Pyruvate to Acetyl CoA PDH Pyruvate + NDH+ CoA Acetyl CoA + CO2 + NADH + H+ 3ATP

Formation of Citric Acid In the first step of the citric acid cycle, acetyl CoA donates the acetyl group to oxaloacetic acid to make citric acid. The high-energy bond between the acetyl group coenzyme A makes the addition of the acetyl group to the oxaloacetatic acid possible.

Dehydration/Hydration In the second step if the Krebs cycle, citric acid is rearranged to form isocitric acid. During this reaction water is removed from one carbon atom of citric acid, and then added back to the adjacent carbon atom. This rearrangement is necessary to prepare the molecule for two consecutive decarboxylation steps, both of which will generate usable energy.

Decarboxylation In the third step of the Krebs cycle, the isocitric acid is oxidized and decarboxylated to produce alpha-ketoglutaric acid. The free energy released during this step is used to reduce an NAD+ molecule to generate an NADH molecule. The NADH molecule can move on to generate three ATPS through oxidative phosphorylation.

Oxidative Decarboxylation In the fourth step of the Krebs cycle, alpha-ketoglutaric acid loses another carbon atom in the form of carbon dioxide. Since the loss of a carbon dioxide molecule is accompanied by a large release of energy, another NADH molecule is generated from NAD+, and the remaining 4-carbon succinyl group is attached to coenzyme A, producing succinyl CoA. This coupling step allows even more energy to be extracted from the succinyl molecule.

In the fifth step of the Krebs cycle, water reacts with succinyl CoA, releasing coenzyme A and producing succinis acid. Breaking the high energy bond between the succinyl group and CoA releases a large amount of energy, which is coupled to the phosphorylation of a guanosine diphosphate molecule to produce guanosine triphosphate. The GTP carries the same amount of energy as an ATP molecule, so it can be used to produce an ATP molecule. The coenzyme A can be recycled back to the previous step to react with an alpha-ketoglutaric acid.

Oxidation The sixth step of the Krebs cycle involves another oxidation reaction, in which succinic acid loses two hydrogen atoms to form fumaric acid. FAD gains these two hydrogen atoms, reducing FAD to FADH2. The FADH2 molecule has the reducing capability to produce two ATP molecules in the oxidative phosphorylation process.

Hydration In the seventh step of the Krebs cycle, the newly created double bond of fumaric acid is hydrated to form malic acid. This step does not produce any energy in itself, but it prepares the intermediate for the next step, which is an oxidation step that will produce energy.

Dehydrogenation In the eighth and final step of the Krebs cycle, a full cycle is reached. Malic acid is oxidized to regenerate oxaloacetic acid, one of the reactants for the first step of the Krebs cycle. At the same time, a molecule of NAD+ is reduced to NADH.

Pyruvate (3C) Acetyl CoA (2C) Citrate (6C) Cis -Aconitate Isocitrate Pyruvate dehydrogenase CoA SH CO2 NAD NADH+H CoA SH Citrate synthase Citrate (6C) H2O Aconitase Oxaloacetate (4C) Cis -Aconitate H2O Aconitase Malate dehydrogenase NAD NADH+H Isocitrate Malate (4C) NADH+H NAD Isocitrate dehydrogenase H2O oxalosuccinate Fumarase CO2 Isocitrate dehydrogenase Fumarate (4C) α-ketoglutarate Succinyl CoA Succinate dehydrogenase NADH+H NAD α-ketoglutarate dehydrogenase CO2 FAD FADH2 CoA SH Succinate (4C) GTP GDP Succinate thiokinase

Summary of the Krebs Cycle One turn of the Krebs Cycle Generates: 2 Carbon dioxide molecules 3 NADH molecules 1 FADH2 molecule 1 ATP molecule TOTAL 4 carbon dioxide molecules 6 NADH molecules 2 FADH2 molecules 2 ATP molecules