Bioenergetics MDSC1101 – Digestion & Metabolism Dr. J. Foster Biochemistry Unit, Dept. Preclinical Sciences Faculty of Medical Sciences, U.W.I.

What do you think “bioenergetics” means? bio = biology energetics = branch of physics that studies energy flow

What then is the significance of “bioenergetics”? Bioenergetics – study of how such energy flows, transforms & is harnessed Processes by which the body meets energy demands e.g. digestion & other metabolism

Bioenergetics The study of transformation and flow of energy within biological systems, and with their environment Concerned with the initial and final energy states of reactants and not the mechanism or kinetics Simply put - biochemical thermodynamics

Bioenergetics Thermodynamics - laws & principles describing the flow and interchanges of heat, energy, & matter in systems Concepts very applicable to biological systems System – portion of the universe we are concerned with Surroundings – everything else!

Systems Three types Isolated - cannot exchange matter or energy with its surroundings Closed - may exchange energy, but not matter, with the surroundings Open - may exchange matter, energy, or both with the surroundings

Garrett, Grisham. Biochemistry, 2nd ed © 2000

What kind of system would you classify the human body as? Justify your choice. Exchanges matter (food in & waste out) Exchanges heat (homeostasis) The human body is an open system

Which laws do you think impact on thermodynamic events within systems? Can you recall any laws of physics that may apply? clue : thermal  heat  energy

Laws of Thermodynamics 1st Law - the total energy of a system (including surroundings) remains constant energy cannot be gained or lost it can be transferred from part to part It can be converted from one form to another What exactly determines how energy flows and whether reactions occur?

Laws of Thermodynamics Gibbs free energy (G) energy available to reactants/products in rxn determines the feasibility of chemical reactions i.e. direction & extent (predictive) Two forms of G used in defining chemical reactions ΔG, the change in G of rxn ΔG°, the standard ΔG (reactants/products@1 mol/L) ΔG° useful only under standard conditions

Laws of Thermodynamics 1st Law - the total energy of a system (including surroundings) remains constant 2nd law - total entropy of a system must increase for a process to occur spontaneously

Free Energy Given a reaction where A ⇆ B, if ΔG is negative – rxn is exergonic*, energy is lost from system, spontaneous from A → B is positive – rxn is endergonic*, energy is required by system from surroundings for rxn to occur equals zero – rxn is at equilibrium; no direction favoured also Δ G A→B = - Δ G B→A Spontaneous reactions equilibrium *differ from exothermic/endothermic which relate to only heat Exergonic/endergonic vs endothermic/exothermic – energy of many forms not only heat!!

Garrett, Grisham. Biochemistry, 2nd ed © 2000

Free Energy ΔG is determined by two factors Enthalpy (ΔH) – change in heat of reactants and products of a rxn (e.g. chemical bonds) Entropy (ΔS) – change in randomness/disorder of reactants & products Neither ΔH or ΔS can predict rxn feasibility alone

ΔG= ΔH – TΔS as Δ S increases, ΔG becomes more -ve °K = 273 + °C J/mol J/mol/K J/mol as Δ S increases, ΔG becomes more -ve

Free Energy ΔG can also be defined by the concentrations of A & B: ΔG = ΔG° + RT ln [B]/[A] At constant P (pressure) & T (absolute ) – thermal equilibrium R = gas constant (8.315 J/mol/K) In = natural logarithm [B] = concentration of product [A] = concentration of reactant Note that ΔG and ΔG° can have different signs

Free Energy ΔG and ΔG° can differ greatly depending on [A], [B] Under standard conditions [A]=[B]= 1 mol/L ΔG = ΔG° + RT ln [B]/[A] ΔG = ΔG° + RT ln 1 (ln 1 = 0) ΔG = ΔG° ΔG° is predictive only under standard conditions ΔG and ΔG° can differ greatly depending on [A], [B]

Free Energy At equilibrium (steady-state) At equilibrium ΔG = 0 [A] / [B] = constant = Keq Thus, ΔG = ΔG° + RT ln [B]/[A] becomes ΔG = ΔG° + RT lnKeq At equilibrium ΔG = 0 0 = ΔG° + RT lnKeq ΔG° = -RT lnKeq

Bioenergetics of pathways Biochemical pathway - series of rxns each with characteristic ΔG Thermodynamically for a pathway ΔGpathway can be considered additive feasibility depends on sum of individual ΔG’s As long as the sum of ΔG is –ve the pathway is feasible

A rxn can still occur even if ΔG is +ve if it is kinetically favoured… how?? Enzymes – they reduce the activation energy needed for a rxn (kinectics)

Bioenergetics of pathways Many biological systems have rxns that have +ve ΔG How do biological systems overcome +ve ΔG’s? Exergonic reactions are usually coupled with endergonic ones Such coupling of rxns involves using a common intermediate – an energy coupler

E.g. First step of Glycolysis The individual half-reactions in aqueous solution: ATP + H2O  ADP + Pi DGo' = -31 kJ/mol (exg) Pi + glucose  glucose-6-P + H2O DGo' = +14 kJ/mol (end) Hexokinase catalyses rxn (active site excludes H2O & promotes coupled over individual rxns) ATP + glucose  ADP + glucose-6-P DGo' = -17 kJ/mol ATP is thus the coupler for the reaction

Garrett, Grisham. Biochemistry, 2nd ed © 2000

ATP as an energy coupler The energy currency of cells – universal coupler Intermediate in the rank of high-energy phosphates Allows it to accept and donate energy in numerous rxns

ATP as an energy coupler Terminal phosphate bonds are “high energy” (~) i.e. release a large amount of energy on hydrolysis Phosphate bonds allow for ATP to release energy for metabolic processes when hydrolysed to ADP + Pi ADP to store energy from catabolic processes as chemical potential energy in the form of ATP

Harper’s Biochemistry 26th ed, Appleton and Lange, USA

Anabolic – complex molecules from simple ones (endergonic) Catabolic – simple molecules from complex ones (exergonic) ATP bridges the 2 types of metabolism Lehninger, Biochemistry, 4nd edition © 2005

Thermodynamics vs Kinetics A high activation energy barrier usually causes hydrolysis of a “high energy” bond to be very slow in the absence of an enzyme catalyst. Such kinetic stability is essential to the role of ATP and other compounds with ~ bonds

Why is this kinetic stability for ATP hydrolysis a good thing?? Rapid hydrolysis (due to low barriers) would hinder ATP’s role in metabolism enzymes lower these barriers, and most importantly couple the rxn with other useful ones prevents free energy released from ATP hydrolysis being wasted

Redox Reactions Redox (oxidation-reduction) rxns are inherently coupled & involve both donating of e- (oxidation) accepting of e- (reduction) The two halves of a redox rxn are considered separately: Fe2+ + Cu2+ ↔Fe3+ + Cu+ Can be rewritten in half-reactions as Fe2+ → Fe3+ = e- Cu2++ e- → Cu+

Redox Reactions Free energy is also transferred via the movement of these electrons The transfer of e- can be measured as reduction potentials (E) This is the tendency of a chemical species to acquire electrons and thereby be reduced

Redox Reactions For a rxn, E can be used to calculate G: ΔG = -nFΔE likewise, ΔGo = -nFΔEo n = number of electrons transferred, F = Faraday’s constant (96,480 J/V/mol), E = reduction potential Eo = std reduction potential +ve E favours a –ve G (forward rxn) –ve E favours a +ve G (backward rxn)

Summary Organisms are open systems that utilise free energy (in the form of chemical energy) to live Use chemical coupling of spontaneous exergonic rxns to overcome the energy demand of endergonic ones ATP is the most important coupler and acts as energy currency of cells Redox reactions also determined by free energy

Further Reading Harper’s Biochemistry, 26th Ed. - Chapter 10