TCA Cycle L-6 PDF

Tricarboxylic Acid Cycle  The Krebs Cycle Occurs in the matrix of the mitochondria Aerobic phase (requires oxygen) 2-carbon acetyl CoA joins with a 4- carbon compound to form a 6- carbon compound called Citric acid.  Citric acid (6C) is gradually converted back to t...

Tricarboxylic Acid Cycle  The Krebs Cycle Occurs in the matrix of the mitochondria Aerobic phase (requires oxygen) 2-carbon acetyl CoA joins with a 4- carbon compound to form a 6- carbon compound called Citric acid.  Citric acid (6C) is gradually converted back to the 4-carbon compound oxaloacetate. -ready to start the cycle once more The carbons removed are released as CO2 -enzymes controlling this process are called decarboxylases. The hydrogens, which are removed, join with NAD to form NADH2. -enzymes controlling the release of hydrogen are called dehydrogenases.  Link between Glycolysis & TCA Pyruvate, the end-product of aerobic glycolysis, must be transported into the mitochondrion before it can enter the TCA cycle. Once in the matrix, pyruvate is converted to acetyl CoA by the enzyme pyruvate dehydrogenase complex.  TCA CYCLE TCA cycle is so named, because at the start of cycle citrate is formed in which 3 carboxyl groups are present. It is a common pathway for oxidation of carbohydrate, lipid & protein. Metabolic pathways of carbohydrate, lipid & protein end in TCA cycle. TCA cycle oxidizes acetyl CoA to Co2 & H2O  Gluconeogenesis, trans-amination, de- amination & fatty acid synthesis originate from the cycle TCA CYCLE is an amphibolic cycle (It is both Anabolic as well as Catabolic). The intermediates of this cycle form large biomolecules. At the same time large biomolecules like carbohydrate, protein etc break down to smaller molecules. This cycle forms large amount of ATP It also produces many intermediates. Intermediates are required for synthesis of Amino acids, glucose & heme. TCA Cycle is Amphibolic cycle STEP WISE REACTIONS OF TCA CYCLE: Citrate is formed by condensation of Acetyl-Co A & oxaloacetate by citrate synthase. Citrate is permeable across mitochondrial membrane. Aconitase enzyme converts citrate first to cis-aconitate, then to isocitrate. Isocitrate is oxidatively decarboxylated first to oxalosuccinate, then to α- ketoglutarate by enzyme isocitrate dehydrogenase. 1 molecule of NADH+H & Co2 are formed  α-ketoglutarate is oxidatively decarboxylated to succinyl CoA by α- ketoglutarate dehydrogenase complex. Lipoic acid & 4 co-enzymes of vitamins take part, same like pyruvate dehydrogenase complex 1) TPP (B1) 2) FAD (B2) 3) NAD (B3) 4) coenzyme A ( Pantothenic acid ) NADH+H & Co2 are formed  Acetyl-coA Oxaloacetate Malate dehydrogenase Citrate synthase NADH+H Malate Citrate NAD Fumarase Aconitase Fumarate Succinate dehydrogenase Isocitrate FADH2 NAD CO2 FAD Succinate NADH+H Isocitrate dehydrogenase GTP Succinate thiokinase GDP Succinyl-CoA oxalosuccinate Isocitrate dehydrogenase NADH+H a-ketoglutarate NAD α-ketoglutarate dehydrogenase complex CO2  Succinyl CoA is converted to succinate by enzyme succinate thiokinase. GTP is formed, which is converted to ATP Succinate is oxidized to fumarate by succinate dehydrogenase FADH2 is formed Fumarate is converted to malate by fumarase. Malate is oxidized to oxaloacetate by malate dehydrogenase enzyme, with the formation of 1 molecule of NADH+H Energy formation by 1 molecule of Acetyl Co-A in TCA Cycle Iso-citrate-dehydrogenase NADH = 3 ATP α-ketoglutarate dehydrogenase NADH = 3 ATP Succinate thiokinase ATP = 1 ATP Succinate dehydrogenase FADH2 = 2 ATP Malate dehydrogenase NADH = 3 ATP  Energy yield by 1 molecule of glucose after passing through aerobic glycolysis & TCA cycle 1) Through aerobic glycolysis = 8 ATP 2) Oxidative decarboxylation of 2 Pyruvic acids to 2 Acetyl CoA = 2x 3 = 6 ATP 3) Oxidation of 2 Acetyl CoA in TCA cycle = 2x12 = 24 ATP ---------------------- TOTAL = 38 ATP Under anaerobic condition 2 ATP only.  The TCA cycle (Overview) It is a cyclic pathway. All intermediates are derivatives of citric acid, a tricarboxylic acid Total of 8 steps. Acetyl CoA, a 2 carbon molecule enters the cycle by condensation with the 4- carbon oxaloacetate. Each of the two carbons of acetyl CoA are oxidized and removed as CO2 in two separate reactions. Oxaloacetate is regenerated.  3 molecules of NAD+ are reduced to 3 molecules of NADH + H+. one molecule of FAD is reduced to FADH2 one molecule of GDP is phosphorylated to GTP. This is called substrate level phosphorylation (as opposed to oxidative phosphorylation).  Anabolic role of TCA cycle large biomolecules like protein, carbohydrate & lipids are finally broken down in the TCA cycle. Intermediates of the TCA cycle serve as precursors for biosynthesis of biomolecules Many aminoacids are synthesized starting with transamination of α- ketoglutarate Porphyrins and heme are synthesized from succinyl CoA.  Oxaloacetate is another α-keto acid and its transamination leads to aspartate and other amino acid biosynthesis. Oxaloacetate is also the precursor of purines and pyrimidines via aspartate. Fatty acids and sterols are synthesized from citrate.  Few important points TCA cycle is also known as Krebs cycle or Citric Acid cycle. Occurs in the matrix of the mitochondria. Pyruvate is the link between Glycolysis and TCA cycle. TCA cycle is so named, because at the start of cycle, citrate is formed in which 3 carboxyl groups are present. It is a common pathway for oxidation of carbohydrate, lipid & protein.  TCA CYCLE is an amphibolic cycle (It is both Anabolic as well as Catabolic). The intermediates of this cycle form large biomolecules. At the same time large biomolecules like carbohydrate, protein etc break down to smaller molecules to form intermediates of this cycle. Porphyrins and heme are synthesized from succinyl CoA. Fatty acids and sterols are synthesized from citrate.  Total No of ATP formed by 1 molecule of Acetyl CoA in TCA cycle is = 12 ATP. Total No of ATP formed by 1 molecule of Glucose after passing through Aerobic Glycolysis and TCA is = 38 ATP.