Krebs cycle/ TCA Cycle/ Citric Acid Cycle/ Tri Carboxylic Acid Cycle/ CAC

1. The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle– is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.

2. For each turn of the cycle, three NADH, one ATP( through GTP) and one FADH2 are created.

1. KREB’S CYCLE Rajdip Majumder Tutor, Institute of Nursing, Brainware University

2. Introduction Also known as citric acid cycle or TCA cycle(Tri carboxylic acid) cycle. The pyruvate molecules released during glycolysis are transported across the mitochondrial membrane into the inner mitochondrial matrix , where they metabolized by the enzymes called the Krebs cycle. During the cycle high energy molecules are created like ATP, NADH and FADH2. The purpose is to generate more ATP.

3. Introduction The primary function of TCA cycle is to provide more energy in the form of ATP. It is a final and common pathway for oxidation of carbohydrate, lipid and protein via acetyl CoA. The three carbon pyruvate molecules generated during glycolysis moves from the cytoplasm into the mitochondrial matrix, where it is converted by the enzyme pyruvate dehydrogenase into a two carbon acetyl coA molecules. This is the decarboxylation reaction. So the acetyl coA enters the krebs cycle by combining with a four carbon molecule, oxaloacetate, to form the six- carbon molecule citrate or citric acid.

4. Reactions of TCA cycle Step:1 Formation of citrate Oxaloacetate condenses with acetyl CoA to form Citrate , catalysed by the enzyme citrate synthase. Steps 2 & 3 Citrate is isomerized to isocitrate Citrate is isomerized to isocitrate by the enzyme aconitase Steps 4 & 5 Formation of α - ketoglutarate Isocitrate dehydrogenase (ICDH) catalyses the conversion of (oxidative decarboxylation) of isocitrate to α - ketoglutarate . The formation of NADH & the liberation of CO2 occur at this stage.

5. Step: 6 Conversion of α - ketoglutarate to succinyl CoA Occurs through oxidative decarboxylation, catalysed by α - ketoglutarate dehydrogenase complex . At this stage of TCA cycle, second NADH is produced & the second CO2 is liberated. Step: 7 Formation of succinate Succinyl CoA is converted to succinate by succinyl - CoA synthetase (Succinate thiokinase ). This reaction is coupled with the phosphorylation of GDP to GTP. GTP is converted to ATP by the enzyme nucleoside diphosphate kinase.

6. Step: 8 Conversion of succinate to fumarate Succinate is oxidized by succinate dehydrogenase to fumarate . This reaction results in the production of FADH2 . Step : 9 Formation of malate: The enzyme Fumarase catalyses the conversion of fumarate to malate. Step:10 Conversion of malate to oxaloacetate Malate is then oxidized to oxaloacetate by malate dehydrogenase . The third & final synthesis of NADH occurs at this stage . The oxaloacetate is regenerated which can combine with another molecule of acetyl CoA & continue the cycle.

7. Significance of TCA cycle: Complete oxidation of acetyl CoA . ATP generation . Final common oxidative pathway . For each turn of the cycle , three NADH, one ATP( through GTP) and one FADH2 are created . Excess carbohydrates are converted as neutral fat.