BC351 Lecture 11 Metabolism TCA Cycle Terms Cellular respiration Principles 1 Cellular respiration a Cellular respiration is a central process of metabolism in the majority of organism known to man b It is not exclusively run for glucose Fatty acid and amino acid catabolism feed into this process 2 REDOX a Glucose combustion is a redox reaction b Glycolysis had a single dehydrogenase c The 1st two phases of cellular respiration contain 5 dehydrogenases out of only 9 enzymes d CO2 will be produced I Overview pgs 615 616 a Cellular respiration i Definition of Cellular respiration 1 ATP NADH LN09 GLYCOLYSIS C6H12O6 6O2 NADH FADH2 LN11 TCA Pyruvate ATP NADH FADH2 6H2O 6CO2 G 2840 kJ mol ATP LN12 O P b Three phases i Production of acetyl CoA and CO2 1 Redox 2 Produces electron carriers LN11 1 ii Acetyl CoA oxidation 1 This is the TCA cycle 2 Produces electron carriers CO2 and ATP equivalents iii Oxidative phosphorylation 1 Redox 2 Electron carriers give up their electrons 3 All of three phases takes place in the matrix of the mitochondria II Production of acetyl CoA pgs 616 620 a Pyruvate Dehydrogenase Complex PDH i The reaction G 0 kJ mol 1 Oxidative decarboxylation a NADH and CO2 2 Irreversible step and it is tightly controlled LN11 2 3 Storing energy in a thioester bond Pyruvate HS CoA NAD G 33 kJ mol Acetyl S CoA NADH CO 2 G Acetate HS CoA NADH CO 2 R C ii The enzyme 1 The enzyme is a HUGE complex of multiple copies of three different subunits a E1 Pyruvate dehydrogenase b E2 Dihydrolipoyl transacetylase c E3 Dihyrolipoyl dehydrogenase 2 Vitamins as coenzyme derivatives a NAD and niacin b FAD and riboflavin c TPP and thiamine d Coenzyme A and Panthoic acid LN11 3 III The Citric acid cycle pgs 620 631 a Overview i 8 new enzymes 1 4 out of 8 enzymes are dehydrogenases 2 Reduced electron carries will be produced ii Run two times glucose iii Starting materials 1 One acetyl CoA molecule and one oxaloacetate OAA molecule iv Ending material 1 One OAA molecule 2 Carbons are lost as CO2 throughout LN11 4 b Reaction one Citrate synthase i The reaction Free energy G CITRATE SYNTHASE G 0 kJ mol ACETYL CoA OAA CITRATE CoA 1 Combines oxaloacetate OAA 4 carbons with acetylSCoA 2 carbons to make citrate 6 carbons 2 Irreversible reaction G 0 a Despite very low OAA b Reaction is driven by free energy difference b w reactants and products c Reaction Two Aconitase i The reaction 1 Converts citrate to isocitrate 2 Reversible d Reaction three Isocitrate dehydrogenase i The reaction G 0 kJ mol 1 Redox a Production of CO2 b NAD reduced to NADH LN11 5 G 0 kJ mol e Reaction four ketoglutarate dehydrogenase complex i The reaction G 0 kJ mol 1 Redox again a Production of CO2 b NAD reduced to NADH 2 This enzyme is almost identical to PDH in both structure and mechanism 3 Energy is once again stored in a thioester bond f Reaction five Succinyl CoA synthetase i The reaction Succinyl CoA GDP Succinate CoA Pi Succinyl CoA GDP Pi GTP GTP Succinate G 33 4 kJ mol G 30 5 kJ mol CoA G 2 9 kJ mol G 0 kJ mol 1 Converts succinyl SCoA to succinate 2 GTP production a This molecule conserves the energy of the thioester that was produced in the KGA reaction b The energy to make that thioester was derived from the redox potential of KGA vs NAD LN11 6 g Reaction six Succinate dehydrogenase i The reaction ALKANE ALKENE FAD FADH2 NAD NADH G 0 kJ mol ALCOHOL KETONE ALDEHYDE 1 Converts succinate to fumarate 2 Succinate is oxidized a FAD is reduced 3 The enzyme a A component of the electron transport chain 4 FAD vs NAD a FAD is used primarily when an alkane is converted to an alkene b NAD is used primarily when an alcohol is converted to a ketone or an aldehyde h Reaction seven Fumerase i The reaction 1 Fumarate to malate G 0 kJ mol LN11 7 i Reaction eight Malate dehydrogenase i The reaction 1 Converts malate to OAA a NAD is reduced 2 G 29 7kJ mol a G 0 b To do this Q must be very small and very little product must be present This is why OAA is so low in the cell and of course this affects the Q of the 1st reaction of the cycle CITRATE SYNTHASE G 0 kJ mol Free energy G Free energy G MALATE DEHYDROGENASE G 0 kJ mol Q L MALATE Keq Q OAA ACETYL CoA OAA LN11 8 CITRATE CoA IV Citric acid cycle regulation pgs 635 637 a Allosteric modulation of the TCA cycle i Allosteric negative modulation of the TCA cycle 1 Specifically by a ATP i High levels of ATP are indicative of a high EC and as such a catabolic pathway is expected to be down regulated b NADH ii Allosteric positive modulation of the TCA cycle 1 Specifically by a AMP ADP i High levels of AMP ADP are indicative of a low EC and as such a catabolic pathway is expected to be up regulated LN11 9