L15. Metabolism and Thermodynamics BCH210H F24 Patterson PDF

INTRO TO METABOLISM Essential Bio-chemistry – it’s not just about breaking down molecules… Sian Patterson, Ph.D. Associate Professor, Teaching Stream  For final & assignment INTRO TO METABOLISM Essential Bio-chemistry – it’...

INTRO TO METABOLISM Essential Bio-chemistry – it’s not just about breaking down molecules… Sian Patterson, Ph.D. Associate Professor, Teaching Stream  For final & assignment INTRO TO METABOLISM Essential Bio-chemistry – it’s not just about breaking down molecules… Sian Patterson, Ph.D. Associate Professor, Teaching Stream  Lecture Objectives By the end of this lecture, students should be able to: Compare the features of anabolic and catabolic pathways. Explain the general organization and regulation of enzymes within pathways. Review thermodynamics in the context of enzymes and pathways and predict favourable reactions. Describe the importance of phosphoryl transfer potential for high energy molecules. 2  cofactors cycle of making a breaking down I have no conflict of interest to declare, nor am I a MD. Make your own educated decisions about 3 whether or not you need to take vitamins!  small small - large large - > Catabolism and Anabolism are Interrelated oxidation reduction NADH converts FADH2 put in releasing free energy energy 4  many complex pathways linking together dot molecule : Metabolism is highly complex Check out: https://www.roche.com/sustainability/philanthropy/science_education/pathways.htm 5  CARBOHYDRATES GLYCOGEN LIPIDS GLYCEROL GLUCOSE FATTY ACIDS ENERGY GNG Glycolysis ATP CO 2 PYRUVATE LACTATE PROTEINS Beta Oxidation AMINO ACIDS ACETYL-COA KETONE BODIES & CHOLESTEROL N A D H Citric FA Urea D Acid H2 Cycle Cycle Oxidative Phosphorylation NH 3 CO 2 O2 H2 ATP O 6  Catabolism Bioenergetics and Metabolism Metabolism involves the catabolism of compounds, releasing free energy which can be used to generate ATP. Energy is used in anabolic reactions to synthesize larger macromolecules using simple building blocks. The complex metabolic map can be broken down into linear, cyclic or even branched pathways. Gibbs free energy changes (and enzymes) influence the metabolic flux or the conversion of metabolites through the pathways. 7 catabolize or anabolize does to cell want  Rank the following in terms of importance of determining the flux through a metabolic pathway in a cell: ATP availability infuence Gibbs tree energy ↳ 2. Changes in Gibbs free energy is The presence of enzymes make Metabolite concentration a it new spontenous/favorable favorable ran. 8  Review of a Chemical Reaction TS( */I) A Draw: prometes conversion substrate to product Progress curve for - overs a favourable reaction Energy Label the substrate, AG product and the Gibbs transition state product What happens if an enzyme is present? - What is ∆G? Reaction progress Reaction progress 9 curve Gibbs Free Energy and Reactions Substrate Product Standarda ↳ conditions ΔG = ΔGº′ + RT ln [P] conc in celt [S] Gibbs Free Standard Free °K Energy Energy Change standard Change (1M, 298K, pH 7) condition 8.314 J/molŸK in a cell What does uxn. gas constant Conc. at equilibrium do in standal 10 condition co external - vanables  start with : LPT = IM [S] = IM Standard Free Energy Change set it to 0 rearrange O When ΔG = 0: ΔGº′ = - RT ln Keq’ + Keq’ = [P] [S] f)( +) = E) If Keq’ > 1, ΔGº′ is negative, reaction is exergonic more than S @ ea If Keq’ < 1, ΔGº′ is positive, reaction is endorgonic moves @ eq. ↳ preferes oppositen If Keq’ = 1, ΔGº′ = 0, reaction is reversible S = P 11  Actual Free Energy Change Substrate Product ΔG = ΔGº′ + RT ln [P] in a cell [S] in cell (Uxu ) as written (makeproduct Negative ΔG – exergonic favorable. = Positive ΔG – endergonic unfavorable (prefers opposite = Reactions can be reversible if ΔG = 0 in a cell. It’s the concentrations of substrates and products that determine the directionality to overcome an unfavourable standard ΔGº′. either direction 12 Thermodynamics and Biochemical Reactions The Gibbs free energy under standard conditions (ΔGº′ - 1M, 298K, pH 7.0) depends on the nature of the reactants and their concentrations at equilibrium (K’eq). more orp The cellular Gibbs free energy (ΔG) is dependent on no enzymes the cellular concentrations of substrate and product and ΔGº′. An enzyme can couple a favourable and unfavourable reaction to produce an overall favourable reaction. what's not normally promote favorable 13  Coupled Reactions (or Pathways) Enzyme A + B C + D - endorgonic/unfoorable A C ΔGº′ = + 14 kJ/mol > -exergonis favorable B D ΔGº′ = - 31 kJ/mol - ATD = - TS A+B X‡ C+D ΔGº′ =. 17kJ/mol - Kandnew reacta net ↑ , favorable , exogenic 14  ATP Phosphoryl Transfer Potential 2 ΔGº′ Ho of : hydrolysis ATP + H2O ADP + Pi - 31 kJ/mol very favorable I ADP + H2O AMP + Pi - 36 kJ/mol AMP + H2O Adenosine + Pi - 14 kJ/mol PPi + H2O 2 Pi - 34 kJ/mol The hydrolysis of the different phosphoanhydride bonds release different amounts of free energies due to stabilization of the products. 15 ATP negative charges repel ΔGº′ ↓ ATp is 61 ( unstable R repulsion of - 31 kJ/mol hydrolysis ADP P t ADP T ↳ less repulsion, very stable stable - 36 kJ/mol more AMP products more ar 16 P : has 3 pka valus cus of resonance up very stable Resonance Stabilization 17  ATP Phosphoryl Transfer Potential ΔGº′ ATP + H2O ADP + Pi - 31 kJ/mol very stable ADP + H2O AMP + Pi - 36 kJ/mol E release AMP + H2O Adenosine + Pi - 14 kJ/mol less ① PPi + H2O 2 Pi - 34 kJ/mol 2 linked phosphates The change in free energy can be used to activate molecules for reactions that are highly unfavourable or found in anabolic pathways. uses ATP Caveat - how ATP and ADP are remade from ADP or AMP for future use… 18 & hard to regenerate  Review - ATP Nucleotide made of adenine, ribose and three phosphates. α, β and γ phosphates: linked by phosphoanhydride bonds and an ester bond to the sugar. Involved in both catabolic pathways (breakdown) and anabolic pathways (synthesis) via phosphate group transfer reactions. coupled The change in free energy is dependent on the structures and stability of the substrates and products. depends or molecule condition Free energy changes are not fixed, the polar phosphates are ionizable and pH dependent, while metal ions (Mg2+) also help with stabilization. stablize p- 19  Compounds with similar phosphoryl transfer potentials Nucleoside ob diphosphokinase GTP + ADP - ATP + GDP & ΔGº′ = 0 reversible we loss) energy K′eq = 1 amount all have same 20 of energy coupled n. ⑳ Muscle Contraction ATPase ATP + H2O ADP + Pi + H+ + energy musle can contract 21  Phosphoryl Transfer Potential in Muscle ΔGº′H O= - 43 kJ/mol for phosphate coupled storage form Y phosphorylatex 2 ↑ to ATP Creatine production that + 10 - 0 + Cr so can be ATp [ be Creatine > - can made made from amino acids musch kinase contraction Phosphocreatine + ADP + H+ ATP + Creatine exercise > - 22 I rest acttp] What is the standard free energy change for the phosphate transfer reaction catalyzed by creatine kinase, regenerating ATP? A) - 43 kJ/mol B) - 31 kJ/mol C) - 12 kJ/mol D) + 12 kJ/mol ADD + > - ATP + #x 16 % = + 31k5/mo hophmatinine AG" 23 = 43kJ/mo -Creative - 12" = +12k5(ma favorable  Creatine Kinase Reversibility Creatine kinase ADP + Phosphocreatine ATP + Creatine - AG"= - 12kJ/mot ΔG overall = ΔGº′ + RT ln [ATP][creatine] [ADP][phosphocreatine] to reverse ↑[ATP] 24  Lecture Summary Metabolism consists of catabolic (energy producing) and anabolic (building) pathways. Thermodynamics is the driving force behind the spontaneity of metabolic reactions. The flux of the pathways can also be influenced by enzyme regulation, leading to the production of other metabolites. ATP and other high energy intermediates, as well as metabolite concentrations can drive unfavourable reactions in the forward direction, achieving the cell’s ultimate goal (catabolism vs. anabolism). 25