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Welcome to Metabolism….. Time to put some LIFE into the subject What is Life? What are the properties of life? Movement Turnover of components Reproduction of one’s kind Energy Transformations Chemical Energy is the Dominant Energy Form in a Living System Metabolism: The process by which a living system derives or uses energy through chemical change Energy A B Anabolism: Synthesis. Putting free energy to work Endergonic Catabolism: Degradation. Deriving free energy Exergonic ATP: Energy currency. The standard that is used to gauge all energy compounds The 5 Rules of Energy Metabolism Rule: Living system are able to conserve energy Rule: Heat is wasted energy Heat is energy that cannot be conserved Rule: Living systems will do their utmost to prevent lost of free energy as heat Rule: Exergonic biochemical transformations channel a large part of the free energy into chemical bonds of the product. Rule: Catabolic reactions drive anabolic reactions O O O HO-P-O~P-O O O C ~O-P-O O O Phosphoanhydride bond + NH2 O Acylphosphate bond (mixed anhydride) C HO-P~ NH O High Energy Compounds N CH2-COO- CH3 Nitrogen-Phosphate bond Phosphocreatine Enol-phosphate bond OOC O C~O-P-OH CH2 O O Phosphoenol pyruvate (PEP) Thioester bond CH3-C~S-CoA Acetyl-Coenzyme A (Acetyl-CoA) See Strategies p.173-174 Careful- Phosphate Esters are Not High Energy! -CH2O H Alcohol O Water + HO P OH O Acid Phosphate ester (low energy) Putting High Energy Concepts to Work O Low energy phosphate ester C H + ADP H- C-OH O NO REACTION CH2O-P O Glyceraldehyde O 3-PO4 O High energy phosphoanhydride O C O-P-O O + ADP H- C-OH O CH2O-P O 1,3-bisPO4 O glycerate O C O H- C-OH O + ATP CH2O-P O O WHY? Chemical reactions depend on breaking and making bonds Breaking a bond makes energy available to make a bond Breaking a phosphate ester bond (low energy) does not release energy sufficient to make an phosphoanhydride bond (high energy) ERGO: You can’t use a spitball to fire a cannon Coupled Reactions Glucose + Pi ATP + H2O Glucose-6-P + H2O Go’ = +13.8 kJ/mol ADP + Pi Go’ = - 30.5 kJ/mol Coupling depends on a common intermediate in both reactions Glucose + Pi Glucose-6-P + H2O ATP + H2O ADP + Pi Glucose + ATP Glucose-6-P + ADP Go’ = - 16.7 kJ/mol Anaerobic Aerobic Oxidized cofactors (recycle back Reduced cofactors (drive Ox Phos) The Glycolysis Pathway • • • • • Major anaerobic pathway in all cells NAD+ is the major oxidant Requires PO4 Generates 2 ATP’s per glucose oxidized End product is lactate (mammals) or ethanol (yeast) • Connects with Krebs cycle via pyruvate Glycolysis Two Stages a-D-Glucose OH 1. Hexose stage 2. Triose stage Hexose CH2OH O Hexokinase Glucose-6-Phosphate ATP CH2OPO3 O OH Phosphoglucoisomerase Fructose-6-Phosphate CH2OPO3 O CH2OH OH CH2OPO3 O CH2OH Fructose-6-Phosphate OH ATP Phosphofructokinase-I CH2OPO3 O CH2OPO3 Fructose 1,6-Bisphosphate OH CHO CH2OPO3 C=O Aldolase CH2OH Dihydroxyacetone-Phosphate H-C-OH CH2OPO3 Glyceraldehyde-3-Phosphate Hexose Stage Reactions CHO OPO3 2OH Fructose-6-Phosphate C-OH =O Glucose-6-Phosphate HO-C C-OH Fructose 1,6-Bisphosphate C-OH CH2OH PO3 Phosphoglucoisomerase HEXOKINASE Phosphofructokinase-I o G Kj/mol Goo= -14.2kJ/mol kJ/mol G == -16.7 +1.7 ATP Preparing for the Triose Stage ALDOLASE Fructose 1,6bisphosphate CH2OP C=O HO-C-H .. H-C-OH C-OH CH23OH PO3= CH2OP C=O CH CH23OH DihydroxyAcetone Phosphate CH2OP C=O HO-C-H .. H + CHO H-C-OH Dihydroxy Acetone Phosphate (DHAP) C-OH CH2OP Glyceraldehyde-3-P Triose Stage Dihydroxy acetone phosphate (DHAP) CH2OPO3 CHO Glyceraldehyde 3-phosphate H-C-OH C=O CH2OH CH2OPO3 Triose phosphate isomerase CHO PO4 H-C-OH CH2OPO3 NAD+ Glyceraldehyde-3-P Dehydrogenase O C ~OPO3 COO H-C-OH ADP CH2OPO3 NADH + H+ 1,3 bisphosphoglycerate H-C-OH ATP CH OPO 2 3 3-phosphoPhosphoglycerate glycerate Kinase COO COO H-C-OH H-C-OPO3 CH2OPO3 3-PGA -H2O C~OPO3 PEP CH2OH 2-PGA Phosphoglyceromutase COO CH2 ADP Enolase Pyruvate kinase ATP Back to Glycolysis COO NADH + H+ COO C=O HO-C-H CH3 L-lactate NAD+ CH3 Pyruvate