BC351 Lecture 9 Metabolism Glycolysis GNG Terms Irreversible reaction Isozyme Kinase Phosphotase Near equilibrium reaction Principles 1 Glucose combustion is a redox reaction a Metabolism is a long series of reactions that will result in the complete combustion of glucose 2 Thermodynamics of the reactions a At standard conditions b At actual conditions c And of course energy conservation 3 Glucose production I Glycolysis introduction pgs 527 531 a Glucose metabolism i Four fates of glucose LN09 1 b Glucose combustion ATP NADH LN09 GLYCOLYSIS LN11 TCA Pyruvate C6H12O6 6O2 NADH FADH2 ATP NADH FADH2 6H2O 6CO2 G 2840 kJ mol ATP LN12 O P i Glycolysis as the beginning 1 Overview a 10 reactions 10 enzymes i All take place in the cytosol b Two phases i Prep phase ii Payoff phase c Lactic acid Fermentation the 11th reaction LN09 2 II Prep phase pgs 531 535 a Overview i 5 steps 5 enzymes ii Utilized 1 One 6 carbon molecule glucose is what we will go over a Other 6 carbon molecules can feed into this pathway such as i Galactose mannose and fructose 2 2 ATP iii Produced 1 Two 3 carbon molecules glyceraldehyde 3 phosphate 5 steps 5 enzymes C6H12O6 2ATP 2GAP 3C 2ADP Glucose Galactose Mannose Fructose b Reaction one Hexokinase i Definition of a kinase principle 1 1 ii The reaction 1 An overview of reaction layout in your book LN09 3 Principles for Hexokinase 1 Kinases 2 Conservation of free energy 3 G vs G 4 Irreversible reactions 5 Phosphorylated Intermediates iii Conservation of ATP free energy Principle 2 glucose Pi G6P ATP glucose ATP G 13 8 kJ mol ADP Pi G 30 5 kJ mol ADP G6P G 16 7 kJ mol iv Actual free energy vs Standard free energy Principle 3 1 For this reaction at conditions prevailing in the cell the actual free energy is a G 33 9 2 What does this tell us about Q or the ratio of product reactants in the cell a Is it larger than Keq or smaller b Is it smaller than 1 0 G 33 9 kJ mol G 33 9 kJ mol Pure reactant Free energy G G 16 7 kJ mol Free energy G G 16 7 kJ mol 1 1 Pure product Q Pure reactant 1 1 Keq Pure product v Irreversible reactions Principle 4 1 Definition of irreversible reaction a b The driving force for these reactions is in the direction of products at cellular conditions c These types of reaction are often called far from equilibrium LN09 4 vi G6P represents a phosphorylated intermediate Principle 5 1 Back to the conservation of energy a G6P s free energy is higher than Glucose b This gain in free energy was derived from ATP G R C 2 Can t leave a The need for a phosphotase i Definition of phosphotase 1 ii The liver cell is unique in this sense c Reaction two Phosphohexose isomerase i The reaction Principles for Phosphohexose isomerase 1 Near equilibrium reactions a Thermodynamics b Favored direction 1 Standard free energy only slightly favors reactants at equilibrium LN09 5 ii Near equilibrium reactions 1 Actual free energy is a G 0 Principle 1a b This is indicative of a reaction is sitting at equilibrium G 1 7 kJ mol G 0 kJ mol Free energy G Free energy G G 1 7 kJ mol G 0 kJ mol Q Pure reactant 1 1 Pure product 1 1 Keq Pure reactant Pure product 2 So where then is the driving force a Mass action Principle 1b G6P F6P G 0 kJ mol b These reactions are often called reversible or near equilibrium reactions 3 Definition of a near equilibrium reaction a LN09 6 d Reaction three Phosphofructokinase 1 PFK 1 i The reaction 1 F6P is converted to fructose 1 6 Principles for PFK 1 1 The committed step 2 Energy conservation in F16BP bisphosphate F 1 6 BP 2 Standard free energy favors products at equilibrium 3 Actual free energy is a G 22 kJ mol b This is an irreversible reaction ii The committed step principle 1 a The carbons that undergo this reaction will become one of the end products Ribose 5 phosphate Glucose G6P F6P F16BP Glycogen b This is a regulation checkpoint meaning that i The cell has mechanisms for turning PFK 1 irreversible reaction on and off LN09 7 iii Energy conservation in F16BP Principle 2 1 How does the free energy of F 16 BP compare to glucose and the other metabolic intermediates F16BP G G6P F6P Glucose a Intrinsic energy in the redox potential of each carbon plus the energy derived from ATP e Reaction four Aldolase i The reaction 1 F 1 6 BP 6 carbons is converted to Glyceraldehyde 3 phosphate GAP 3carbons and Dihydroxyacetone phosphate Principles for Aldolase 1 Stiochiometry of glycolysis 2 A positive standard free energy a The mass action ratio DHAP 3 carbons ii Stiochiometry of glycolysis Principle 1 1 The sugar has been split 2 From here on out everything needs to be doubled a All the way through lecture 11 and the TCA cycle LN09 8 iii Standard free energy is 1 G 23 9 kJ mol Principle 2 2 Actual free energy is a G 0 kJ mol b What does this tell us about the Q Principle 2a Free energy G G 23 8 kJ mol G 0 kJ mol 1 1 Pure reactant Pure product product reactant f Reaction five Triose phosphate isomerase i The reaction 1 DHAP is converted to GAP LN09 9 g Prep phase is done 2 irreversible 5 steps 5 enzymes C6H12O6 2ATP 3 reversible 2GAP 3C 2ADP Energy conserved in i One 6 carbon sugar has been converted to two GAP 3 carbons ii Two ATP molecules were used to do so 1 ATP invested has raised the free energy of the final 3carbon intermediates a It has been conserved b Chemical to chemical conservation III Payoff phase pgs 535 539 a Reaction six Glyceraldehyde phosphate dehydrogenase GAPDH i The reaction 1 GAP is converted to 1 3bisphosphoglycerate 1 3 BPG 2 Standard free energy is a G 6 3 kJ mol 3 Actual free energy is a G 0 kJ mol LN09 10 Principles for GAPDH 1 Our 1st DH reaction 2 Conservation of energy in thioesters ii Dehydrogenation Principle 1 1 Movement of 2 e and 2 H 2 What is oxidized and what is reduced iii Conservation of free energy in thioesters Principle 2 1 The reaction takes place in two stages a To make 1 3 BPG you must 1st i Oxidize the GAP and reduce NAD 1 This has a free energy change of G 1 3 BPG NADH GAP P i NAD G 43kJ mol b You must then make the acyl phosphate bond i This reaction if the energy in the redox R C reaction isn t captured has a very positive free energy change G 49kJ mol c How then is the free energy of the redox reaction captured effectively bridging the free energy of the reactants and products LN09 11 2 …