Voet, Fundamentals, 3rdhttp://www.genome.ad.jp/kegg/pathway/map/map01100.htmlChapter 14Basic principles of pathway chemistry1. Chemical reactions (Chemistry)Most biologically important reactions are group transfer reactions, oxidation-reduction reactions, elimination (dehydration decarboxylation) isomerization(dehydration, decarboxylation), isomerization, rearrangement, carbon-carbon bond chemistry.2. Energy balance (Thermodynamics, Kinetics)Pathway catalysis is determined by the activation energy, temperature, substrate concentration.3.Cellular integration(Transport, uptake, and secretion of3. Cellular integration(Transport, uptake, and secretion of metabolites) Anabolic and catabolic pathways are often segregated into compartments and cells spend a lot of energy to transport bt t bil i l bsubstrates across biological membranes.4. Control (Regulatory mechanism of pathways) Pathways can be activated and shut down by allosteric yycontrol, modulation of enzyme activity, and enzyme availability (gene expression, translation control).Energy BalanceR ibilit th d i d ilib i f h i l tiReversibility, thermodynamics, and equilibrium of chemical reactionsThe change in Gibbs freeGibbs free energy can be used to measure chemical energy il bl davailable to do workMeasuring the change in Gibbs free energy ΔGLehninger, ch01gggyΔG < 0 spontaneous reactionA generalized energy profile of a chemical reactionVoet, Fundamentals, 3rdFig 11.5Metabolic pathways operate in small steps l t h i l ilib iclose to chemical equilibriumΔG far away from equilibriumΔG far away from equilibriumΔG close to equilibrium (occasionally an irreversible step (y pincluded)3rded,., 2001Coupling exergonic and endergonic reactions. Here, the first step in Cox, Lehninger, 3glycolysisCh01 CVoet, Fundamentals, 3rdFigure 14-6Factors influencing direction, reversibility, and speedof chemical eesb ty,a dspeedoce careaction:1. Reaction kinetics and removal of Enzyme limited reaction are far from equilibriumproducts in multi-enzyme pathways; steady-state equilibriumSubstrate limited reactions are at or near equilibrium2. Metabolite concentration affect the free energy of a reactionenergy of a reactionΔG = ΔG0I+ RTln{K}Free energy change in dilute water and at Lehninger, ch01standard conditionsMeasuring Gibbs free energy change under standard conditionsCh14 Cox, Lehninger, 3rded,., 2001Chemical reactionsMost biologically important reactions are group transfer reactions, oxidation-reduction reactions, elimination (dehydration, decarboxylation), isomerization, rearrangement, carbon-carbon bond chemistry.Voet, Fundamentals, 3rdhttp://www.genome.ad.jp/dbget-bin/get_htext?ko01000Group Transfer ReactionsFrom: ‘Biochemistry’ Voet&Voet, Fig.15-7a Voet & Voet, Biochemistry, 3rded, chapter 16Enzymes speed up reactions by lowering the activation energy. They do so by binding a substrate with high specificity.Figure 11-7Voet, Fundamentals, 3rdConformation changes in yeast hexokinase on binding glucose. Figure 15-2a(a) Space-filling model of a subunit of free hexokinase.Voet, Fundamentals, 3rdConformation changes in yeast hexokinase on binding glucose. Figure 15-2bVoet, Fundamentals, 3rd(a) Space-filling model of a subunit of hexokinase bound with glucose.Reactions catalyzed by Hexokinase : ITP + D-Glucose=IDP + D-Glucose 6-phosphate;ITP + DGlucose IDP + DGlucose 6phosphate; dATP + D-Glucose = dADP + D-Glucose 6-phosphate; ATP + D-Mannose = ADP + D-Mannose 6-phosphate; ITP + D-Mannose = IDP + D-Mannose 6-phosphate; dATP + DMannose = dADP +DMannose 6phosphate;dATP + D-Mannose = dADP +D-Mannose 6-phosphate; ATP + D-Fructose = ADP + D-Fructose 6-phosphate; ITP + D-Fructose = IDP + D-Fructose 6-phosphate; dATP + D-Fructose = dADP + D-Fructose 6-phosphate; ATP + DGl i ADP + DGl i 6hhtATP + D-Glucosamine = ADP + D-Glucosamine 6-phosphate; ITP + D-Glucosamine = IDP + D-Glucosamine 6-phosphate; dATP + D-Glucosamine = dADP + D-Glucosamine 6-phosphate; ATP + Sorbitol = ADP + Sorbitol 6-phosphate; ITP S bi l IDP S bi l 6hhITP + Sorbitol = IDP + Sorbitol 6-phosphate; dATP + Sorbitol = dADP + Sorbitol 6-phosphate (from
View Full Document
Unlocking...