Krebs Cycle PDF

- It is also known as: 8. Krebs 1– Krebs cycle Cycle Sir Hans Krebs Nobel prize, 1953 2– TCA (tricarboxylic acid) cycle  The citric acid cycle requires aerobic 8. Krebs conditions Cycle - Oxygen serves as the final electron ac...

- It is also known as: 8. Krebs 1– Krebs cycle Cycle Sir Hans Krebs Nobel prize, 1953 2– TCA (tricarboxylic acid) cycle  The citric acid cycle requires aerobic 8. Krebs conditions Cycle - Oxygen serves as the final electron acceptor as pyruvate (from glycolysis) is converted (oxidized) completely to CO2 and H2O  - If cell is under anaerobic conditions energy production is not too efficient. (6 %) 8. Krebs Cycle  Reduced coenzymes NADH and FADH2 8.1 Energy in the citric acid Oxidative phosphorylation to make ATP cycle The Tricarboxylic acid (TCA) cycle (citric acid cycle) is amphibolic  1. Oxidize Acetyl-CoA to CO2 to produce energy 8.2 The TCA Cycle Serves - ATP (GTP) Two Purposes - Reducing power of NADH and FADH2 - The cycle is involved in the aerobic catabolism of carbohydrates, lipids and amino acids  2. Intermediates for 8.2 The TCA biosynthetic reactions Cycle Serves Two Purposes Supply precursors for biosynthesis of carbohydrates, lipids, amino acids, nucleotides and porphyrins.  8.2 The TCA Cycle Serves Two Purposes Cycle intermediates can be shared with other pathways, which may lead to a re-supply with net decrease in cycle intermediates. Reactions feeding into the cycle replenish the pool of cycle intermediates.  8.3 Fundamental Differences between Glycolysis and TCA Cycle 2. Glycolysis occurs in 3. Glycolysis does not 1. Glycolysis is a the cytosol and TCA require oxygen; TCA linear pathway; TCA is in the requires oxygen cycle is cyclic mitochondrial matrix (aerobic). 8.4 Summary of the citric acid cycle For each acetyl-CoA that enters the cycle: (1) Two molecules of CO2 are released (2) Coenzymes NAD+ and FAD are reduced (3) One GDP (or ADP) is phosphorylated (4) The initial acceptor molecule oxaloacetate is reformed 8. Krebs Cycle Krebs Cycle  8. Krebs Cycle Energy of TCA cycle: Each acetyl CoA entering the cycle nets: (1) 3 NADH (2) 1 QH2 (3) 1 GTP (or 1 ATP)  Oxidation of each NADH yields 2.5 ATP Oxidation of each FADH2 yields 1.5 ATP ATP Complete oxidation of 1 acetyl CoA = 10 ATP Calculation - Glucose degradation via glycolysis, citric acid cycle, and oxidative phosphorylation - Complete oxidation of one glucose = 32 ATP ATP Calculation  8.5 Regulation of the Citric Acid Cycle Regulation depends on the ENERGY LEVEL of cells The key is to keep energy level constant (ATP, NADH, FADH2) Krebs are more slowed The reverse is also true 8.5 Regulation of the Pathway controlled by: Citric Acid Cycle (1) Small molecule modulators (products of the cycle can inhibit) (2) Covalent modification of cycle enzymes (3) Supply of acetyl CoA Regulation of Krebs cycle  8.5.1 Regulation of citrate synthase - Inhibitors: NADH, ATP, succinyl-CoA, citrate Regulation of - Stimulators: ADP Krebs cycle 8.5.2 Regulation of isocitrate dehydrogenase (ICDH) - Inhibitors: NADH and ATP - Stimulators: NAD+, ADP and Ca+2  8.5.3 Regulation of α- ketoglutarate dehydrogenase complex Regulation of Krebs cycle - Inhibitors: NADH, ATP and succinyl-CoA - Stimulators: NAD+, ADP, AMP  from Ancient Greek anaplerosis (aná, “up”) (plēróō, “to fill”).  1. Pyruvate Carboxylase converts pyruvate to oxaloacetate. 8.6 Anaplerotic Reactions Replenish Activated by acetyl-CoA increasing the flux through TCA cycle. TCA 2. Degradation of odd numbered Cycle Intermediates: fatty acids yields succinyl-CoA 3. Degradation of amino acids produces other intermediates.