BIOL 3080U: Bioenergetics and Metabolism Lecture Notes PDF

BIOL 3080U: Bioenergetics and Metabolism Chapter 13 - Principles of Bioenergetics Metabolism: Total sum of series of enzymatic pathways that facilitate the build up (anabolic reactions) and breakdown (catabolic reactions) of biomolecules Bioenergetics: Quantitative study of energy t...

BIOL 3080U: Bioenergetics and Metabolism Chapter 13 - Principles of Bioenergetics Metabolism: Total sum of series of enzymatic pathways that facilitate the build up (anabolic reactions) and breakdown (catabolic reactions) of biomolecules Bioenergetics: Quantitative study of energy transduction Questions to address throughout the course of the term in BIO 3080U: 1. Metabolism of biomolecules: carbohydrates, lipids, proteins, nucleic acids – addressing anabolic reactions and catabolic reactions 2. Energy transduction associated with these metabolic processes (i.e. reaction/metabolic pathway is energetically favorable or not) 3. Regulation of mammalian metabolism What dictates whether a metabolic pathway is upregulated, downregulated or inhibited? 2  Metabolism Organic compounds CO2 + O2 Autotrophs Heterotrophs (Use CO2 as sole carbon (Use complex organic source, self-sufficient) molecules as carbon-source) Catabolic rxn Anabolic rxn Anabolic rxn Polymerize Polymerize monomeric precursors Convert nutrients into monomeric precursors to regenerate precursors of to regenerate macromolecules macromolecules for macromolecules energy 3 Metabolism: Total sum of series of enzymatic pathways that facilitate the build up (anabolic reactions) and breakdown (catabolic reactions) of biomolecules Catabolism: Enzymatic pathways that BREAKDOWN and degrade biomolecules (eg. carbohydrates, fats and proteins) Result: simpler, smaller end products (eg. CO2, H2O, NH3) and release of energy Energy in the form of ATP and formation of reduced electron carriers such as NADH, NADPH, FADH2 Anabolism: Enzymatic pathways that result in SYNTHESIS of cellular macromolecules: proteins, polysaccharides, lipids and proteins from precursor molecules (amino acids, sugars, fatty acids and nitrogenous bases) Utilize energy for synthesis of macromolecules Figure 2 Result: oxidized cofactors such as NAD , NADP , FAD, ADP and + + Lehninger Principles of Biochemistry, Eighth Edition © 2021 W.H. Freeman and Company 4 synthesis of cellular macromolecules  We will see Some of the Key-Player Molecules NAD+/NADP+/NADH/NA DPH in numerous metabolic pathways involving oxidation/reduction ATP NAD + / NADH/NADPH reactions NADP+ Major source of energy/fuel for cells! Involved in numerous metabolic pathways either as a product or a substrate 5 Some of the Key-Player Molecules FAD/FMN/FADH2/FMNH2 involved in numerous metabolic pathways that include oxidation/reduction Figure 13.27 reactions Lehninger Principles of Biochemistry, Eighth Edition © 2021 W.H. Freeman and Company 6  Some of the Key-Player Molecules Site of linkage to Coenzyme CoenzymeAA(CoA) (CoA) acetyl- groups 3’ phosphorylated (thioester bond) ADP B- Panthanoic acid mercaptoethylamin e Acetyl-CoA is an important example of a thioester that we’ll see in metabolic pathways 7  Topics for today 1. Bioenergetics Laws of thermodynamics Gibbs free energy Spontaneous vs. non- spontaneous reactions. What determines the direction of a chemical reaction? 2. Different types of metabolic pathways: linear vs. non-linear 3. Common chemical reactions governing metabolic pathways 8 Laws of Thermodynamics Apply to Living Organisms 1.Energy can’t be created or destroyed. Energy can only be converted from one form to another, therefore total amount of energy is always constant in the universe. 2.In all natural processes, the entropy of the universe increases Moves towards an increase in disorder (increase in entropy) 9  Bioenergetics: quantitative evaluation of energy transduction in chemical reactions 3 thermodynamic quantities to recall Gibbs free energy, G: the amount of energy involved during a reaction at constant temperature and pressure - △G’∘  reaction releases energy  exergonic +△G’∘  reaction requires energy  endergonic Enthalpy, H: the heat associated in a chemical reaction -△H  a reacting system that releases heat  exothermic +△H  a reacting system that requires/uptakes heat  endothermic Entropy, S: a measure of randomness and disorder in a system. A reaction system in which the product is more disordered than reactants is considered a reaction that has gained entropy. + △S  entropy gain - △S  entropy loss, product is less disordered 10  What governs the direction of a chemical reaction? Chemical reactions occur to minimize Gibbs Free energy(∆G). Spontaneous reactions are those systems that have a - ∆G. Reactions with a +∆G, require energy and will not spontaneously occur. ∆G is always negative in spontaneous reactions. - ∆H (a reaction that releases heat) & +∆S (an increase in entropy) are conditions that promote a spontaneous reaction. T= temp , kelvin ∆G = ∆H - T∆S < 0 ∆G =Joules/mole or calories/mol ∆H= Joules/mole or calories/mol ∆S =Joules/mole Kelvin We can apply these rules to determine whether a reaction will occur spontaneously, or requires external energy 11 What governs the direction of a chemical reaction? Gibbs free energy is directly associated with the equilibrium constant (Keq) Consider the reaction: aA + bB  cC + dD Keq indicates whether there is more reactant or Keq [Ceq]c [Deq]d product at = [Aeq]a [Beq]b equilibrium Components of (reactants & product) chemical reactions tend to continuously change until equilibrium (rate of forward and reverse reaction is the same, no net change in the system) is reached When a reaction is not at equilibrium, the direction of the reaction can be assessed using change in Gibbs free energy …. How? The magnitude of Gibbs free energy represents the driving force for a reaction to move towards equilibrium 12  What governs the direction of a chemical reaction? Consider the reaction: aA + bB  cC + dD Keq [Ceq]c [Deq]d = [Aeq]a [Beq]b ∆G’o = -RT ln K’eq K’eq = e -∆G’o /RT Spontaneous reaction = K’eq >1, - ∆G’o Important note: ∆G’o : standard free energy change (kJ/mol) Standard conditions: 298K=25oC 1M of initial reactants and products 1 atm (101.3 kPa) pH 7 55.5M water 1mM Mg2+ (ATP as reactant) 13 What governs the direction of a chemical reaction? Under standard conditions, ∆G’o is the difference between the free-energy of products vs. free-energy of reactants -∆G’o : products have less free energy than reactants Reactions proceeds spontaneously towards products…. Why? Because all chemical rxns drive towards a decrease in free energy in the system +∆G’o : products have more free energy than reactants Reaction will go in reverse towards reactants, to decrease free energy in the system 14  G°: G°: DG’o for some Reaction type Hydrolysis reactions (kJ/mol) (kcal/mol) representative Acid anhydrides Acetic anhydride + H2O→2 acetate ATP + H2O→ADP + Pi − 91.1 − 30.5 − 45.6 − 21.8 − 7.3 − 10.9 chemical reactions ATP + H2O→AMP + PPi PPi + H2O→2Pi − 19.2 − 4.6 − 43.0 − 10.3 UDP-glucose + H2O→UMP + glucose 1-phosphate Esters Ethyl acetate + H2O→ethanol + acetate − 19.6 − 4.7 Glucose 6-phosphate + H2O→glucose + Pi − 13.8 − 3.3 Amides and peptides Glutamine + H2O→glutamate + − 14.2 − 3.4 Glycylglycine + H2O→2 glycine − 9.2 − 2.2 Glycosides Maltose + H2O→2 glucose − 15.5 − 15.9 − 3.7 − 3.8 Note: Hydrolysis Reactions Lactose + H2O→glucose + galactose Rearrangements − 7.3 − 1.7 tend to be strongly favorable Glucose 1-phosphateglucose 6-phosphate Fructose 6-phosphateglucose 6-phosphate − 1.7 − 0.4 (Spontaneous), - ∆G’∘ Elimination of water 3.1 0.8 Malate→fumarate + H2O Oxidations with molecular oxygen Glucose + 6O2→6CO2 + 6H2O − 2, 840 − 686 Palmitate + 23O2→16CO2 + 16H2O − 9,770 − 2,338 Table 13.4, Standard Free-Energy Changes of Some Chemical Reactions, 15 Page 469 Standard free energy versus actual free energy △G’◦ = Gibbs free energy under standard conditions (T=298k, 1.0M concentration of each component, pH 7.0, pressure 101.3 kPa etc.) △G’◦ is a measured constant for a given reaction under std. conditions △G = Actual Gibbs free energy change △G is variable and dependent on actual/physiological [reactants] and [products], temperature, pressure [C ]c [ D]d G G '  RT ln [ A]a [ B]b 16  Energetics within the cell are NOT standard The actual free-energy change of a reaction in the cell depends on: The standard change in free energy Actual concentrations of products and reactants For the reaction aA + bB cC + dD: Mass-action ratio, Q [C ]c [ D]d G G '  RT ln [ A]a [ B]b Standard free-energy changes are additive: (1) A  B ΔG’1 (2) B  C ΔG’2 Sum: A  C ΔG’1 + ΔG’2 17  ΔG’o is additive G°: G°: Reaction type (kcal/mol) Example of sequential chemical reactions: hydrolysis (kJ/mol) rxn of ATP coupled with transformation of glucose to G- Hydrolysis reactions 6P Acid anhydrides Acetic anhydride + H2O→2 acetate − 91.1 − 21.8 ATP + H2O→ADP + Pi − 30.5 − 7.3 ATP + H2O→AMP + PPi − 45.6 − 10.9 PPi + H2O→2Pi − 19.2 − 4.6 − 43.0 − 10.3 UDP-glucose + H2O→UMP + glucose 1-phosphate Esters Ethyl acetate + H2O→ethanol + acetate − 19.6 − 4.7 Glucose 6-phosphate + H2O→glucose + Pi − 13.8 − 3.3 Amides and peptides Glutamine + H2O→glutamate + − 14.2 − 3.4 Glycylglycine + H2O→2 glycine − 9.2 − 2.2 Glycosides − 15.5 − 3.7 Maltose + H2O→2 glucose − 15.9 − 3.8 RXN (1) A  B : ΔG’1o, K’eq1 Lactose + H2O→glucose + galactose glucose + Pi  G-6P + H2O ; ΔG’ o = + 13.8 kJ/mol Rearrangements − 7.3 − 1.7 Glucose 1-phosphateglucose 6-phosphate − 1.7 − 0.4 Fructose 6-phosphateglucose 6-phosphate Elimination of water 3.1 0.8 Malate→fumarate + H2O Oxidations with molecular oxygen Glucose + 6O2→6CO2 + 6H2O − 2, 840 − 686 Palmitate + 23O2→16CO2 + 16H2O − 9,770 − 2,338 Table 13.4, Standard Free-Energy Changes of Some 18 Chemical Reactions, Page 469  ΔG’o is additive Reaction type G°: (kJ/mol) G°: (kcal/mol ) Example of sequential chemical reactions: hydrolysis rxn of Hydrolysis reactions ATP coupled with transformation of glucose to G-6P Acid anhydrides Acetic anhydride + H2O→2 acetate − 91.1 − 21.8 ATP + H2O→ADP + Pi − 30.5 − 7.3 ATP + H2O→AMP + PPi − 45.6 − 10.9 PPi + H2O→2Pi − 19.2 − 4.6 − 43.0 − 10.3 UDP-glucose + H2O→UMP + glucose 1- phosphate Esters Ethyl acetate + H2O→ethanol + acetate − 19.6 − 4.7 Glucose 6-phosphate + H2O→glucose + Pi − 13.8 − 3.3 RXN (1) A  B : ΔG’1o, K’eq1 Amides and peptides Glutamine + H2O→glutamate + − 14.2 − 3.4 glucose + Pi  G-6P + H2O ; ΔG’ = 13.8 kJ/mol o Glycylglycine + H2O→2 glycine − 9.2 − 2.2 Glycosides − 15.5 − 3.7 Maltose + H2O→2 glucose − 15.9 − 3.8 RXN (2) B  C : ΔG’2o , K’eq2 Lactose + H2O→glucose + galactose ATP + H2O  ADP + Pi ; ΔG’ o = -30.5 kJ/mol Rearrangements − 7.3 − 1.7 Glucose 1-phosphateglucose 6-phosphate − 1.7 − 0.4 Fructose 6-phosphateglucose 6-phosphate SUM of RXN (1) + (2) : A  C : ΔG’1o + ΔG’1o, K’eq1 X K’eq2 Elimination of water 3.1 0.8 Malate→fumarate + H2O ATP + glucose  ADP + G-6P ; ΔG’ o = -16.7 kJ/mol Oxidations with molecular oxygen Glucose + 6O2→6CO2 + 6H2O − 2, 840 − 686 Palmitate + 23O2→16CO2 + 16H2O − 9,770 − 2,338 Coupling of endergonic and exergonic reactions Table 13.4, Standard Free-Energy Changes of Some Chemical Reactions, 19 Page 469  Figure 3 Lehninger Principles of Biochemistry, Eighth Edition © 2021 W.H. Freeman and Company Metabolic pathways can be linear (eg. glycolysis) and non-linear Figure 2 Lehninger Principles of Biochemistry, Eighth Edition © 2021 W.H. Freeman and Company Non-linear metabolic pathways may be converging, diverging and cyclic. Converging pathways, produce a single end product from multiple starting material (catabolic reactions) Divergent pathways, utilize a single precursor and results in production of multiple end products ( anabolic reactions) Cyclic pathway, starting component is regenerated and helps convert another starting component into a 20 product ( eg. citric acid cycle)  NEXT Lecture- Common chemical reactions 1. Oxidation-reduction reactions 2. Group transfer reactions 3. Hydrolysis reactions 4. Reactions that make or break C-C bonds 5. Internal rearrangement-isomerization, elimination 6. Free radical reactions 21  Practice Study Questions Read Chapter 13 The “assigned problems” are numerous and may be repetitive. Do as many as you need to gain mastery of the individual types of questions. Recommended questions (7th or 8th Ed.): Q 2-7, 9, 12-14, 17, 19, 20 Note: the content for some of these assigned questions (i.e. types of chemical reactions) will be covered next lecture. Refer back to those questions once lecture 3 is complete 22