# Thermodynamics & ATP Review thermodynamics, energetics, chemical sense, and role of ATP.

## Presentation on theme: "Thermodynamics & ATP Review thermodynamics, energetics, chemical sense, and role of ATP."— Presentation transcript:

Thermodynamics & ATP Review thermodynamics, energetics, chemical sense, and role of ATP

Lecture 24 Thermodynamics in Biology

A Simple Thought Experiment

Driving Forces for Natural Processes Enthalpy –Tendency toward lowest energy state Form stablest bonds Entropy –Tendency to maximize randomness

Enthalpy and Bond Strength Enthalpy = ∆H = heat change at constant pressure Units –cal/mole or joule/mole 1 cal = 4.18 joule Sign –∆H is negative for a reaction that liberates heat

Entropy and Randomness

Entropy = S = measure of randomness –cal/deg·mole T∆S = change of randomness For increased randomness, sign is “+”

“System” Definition

Cells and Organisms: Open Systems Material exchange with surroundings –Fuels and nutrients in (glucose) –By-products out (CO 2 ) Energy exchange –Heat release (fermentation) –Light release (fireflies) –Light absorption (plants)

1 st Law of Thermodynamics Energy is conserved, but transduction is allowed Transduction

2 nd Law of Thermodynamics In all spontaneous processes, total entropy of the universe increases

2 nd Law of Thermodynamics ∆S system + ∆S surroundings = ∆S universe > 0 A cell (system) can decrease in entropy only if a greater increase in entropy occurs in surroundings C 6 H 12 O 6 + 6O 2  6CO 2 + 6H 2 O complex simple

Entropy: A More Rigorous Definition From statistical mechanics: –S = k lnW k = Boltzmann constant = 1.38  10 –23 J/K W = number of ways to arrange the system S = 0 at absolute zero (-273ºC)

Gibbs Free Energy Unifies 1 st and 2 nd laws ∆G –Gibbs free energy –Useful work available in a process ∆G = ∆H – T∆S –∆H from 1 st law Kind and number of bonds –T∆S from 2 nd law Order of the system

∆G Driving force on a reaction Work available  distance from equilibrium ∆G = ∆H – T∆S –State functions Particular reaction T P Concentration (activity) of reactants and products

Equilibrium ∆G = ∆H – T∆S = 0 So ∆H = T∆S –∆H is measurement of enthalpy –T∆S is measurement of entropy Enthalpy and entropy are exactly balanced at equilibrium

Effects of ∆H and ∆S on ∆G Voet, Voet, and Pratt. Fundamentals of Biochemistry. 1999.

Standard State and ∆Gº Arbitrary definition, like sea level [Reactants] and [Products] –1 M or 1 atmos (activity) T = 25ºC = 298K P = 1 atmosphere Standard free energy change = ∆Gº

Biochemical Conventions: ∆Gº Most reactions at pH 7 in H 2 O Simplify ∆Gº and K eq by defining [H + ] = 10 –7 M [H 2 O] = unity Biochemists use ∆Gº and K eq

Relationship of ∆G to ∆Gº ∆G is real and ∆Gº is standard For A in solution –G A = G A + RT ln[A] For reaction aA + bB  cC + dD –∆G = ∆Gº + RT ln –Constant Variable (from table) º [C] c [D] d [A] a [B] b }

Relationship Between ∆Gº and K eq ∆G = ∆Gº + RT ln At equilibrium, ∆G = 0, so –∆Gº = –RT ln –∆Gº = –RT ln K eq [C] c [D] d [A] a [B] b [C] c [D] d [A] a [B] b

Relationship Between K eq and ∆Gº

Will Reaction Occur Spontaneously? When: –∆G is negative, forward reaction tends to occur –∆G is positive, back reaction tends to occur –∆G is zero, system is at equilibrium ∆G = ∆Gº + RT ln [C] c [D] d [A] a [B] b

A Caution About ∆Gº Even when a reaction has a large, negative ∆Gº, it may not occur at a measurable rate Thermodynamics –Where is the equilibrium point? Kinetics –How fast is equilibrium approached? Enzymes change rate of reactions, but do not change K eq

∆Gº is Additive (State Function) Reaction A  B B  C Sum: A  C Also: B  A Free energy change ∆G 1 º ∆G 2 º ∆G 1 º + ∆G 2 º – ∆G 1 º

Coupling Reactions Glucose + HPO 4 2–  Glucose-6-P ATP  ADP + HPO 4 2– ATP + Glucose  ADP + Glucose-6-P ∆Gº kcal/mol kJ/mol +3.3 +13.8 –7.3 – 30.5 –4.0 – 16.7

Resonance Forms of P i –– –– –– ––

Phosphate Esters and Anhydrides

Hydrolysis of Glucose-6-Phosphate ∆Gº = –3.3 kcal/mol = –13.8 kJ/mol

High ∆Gº Hydrolysis Compounds ∆Gº = –14.8 kcal/mol = –61.9 kJ/mol

High ∆Gº Hydrolysis Compounds ∆Gº = –11.8 kcal/mol = –49.3 kJ/mol

High ∆Gº Hydrolysis Compounds ∆Gº = –10.3 kcal/mol = –43 kJ/mol

Phosphate Anhydrides (Pyrophosphates) ∆Gº = –7.3 kcal/mol = –30.5 kJ/mol

Thiol Esters ∆Gº = –7.5 kcal/mol = –31.4 kJ/mol

Thiol Esters Thiol ester less resonance-stabilized

“High-Energy” Compounds Large ∆Gº hydrolysis –Bond strain (electrostatic repulsion) in reactant ATP –Products stabilized by ionization Acyl-P –Products stabilized by isomerization PEP –Products stabilized by resonance Creatine-P

“High-Energy” Compounds “High-energy” compound is one with a ∆Gº below –6 kcal/mol (–25 kJ/mol)

High-Energy Compounds

Group Transfer Potential

Lecture 25 Chemical Sense in Metabolism

Making and Breaking C–C Bonds Homolytic reactions Heterolytic reactions

Making and Breaking C–C Bonds Nucleophilic substitutions

Nucleophilic Substitution Reactions S N 1

Carbocation

Common Biological Nucleophiles

S N 2 Nucleophilic Substitution –– ––

Reactivity is S N 2 Reactions

Leaving Group Must accommodate a pair of electrons –And sometimes a negative charge

Major Role of Phosphorylation Converts a poor leaving group ( – OH) into a good one (P i, PP i )

Acid Catalysis of Substitution Reactions This H is often donated by an acidic sidechain of enzyme

Central Importance of Carbonyls 1. Can produce a carbocation 2. Can stabilize a carbanion

Biological Carbonyls

Aldol Condensation

Aldolase Reaction Glycolysis and gluconeogenesis

Claisen Condensation

Thioesters in Biology In thioesters, the carbonyl carbon has more positive character than carbonyl carbon in oxygen ester.

“High-Energy” Thioester Compounds

Coenzyme A

Fatty Acid Metabolism Uses Claisen condensation Thiolase acts in fatty acid oxidation for energy production

Thiolase: Role of Cys-SH

Energy Diagram for Reaction ‡ is the transition state –Pentacovalent carbon, for example

Functional Groups on Enzymes Amino acid side chains – –Imidazole –

Functional Groups on Enzymes Coenzymes/cofactors –Pyridoxal phosphate Metal ions and complexes – Mg 2+, Mn 2+, Co 2+, Fe 2+, Zn 2+, Cu 2+, Mo 3+

Enzyme Inhibitors and Poisons Chelating agents –EDTA (divalent cations) –CN – (Fe 2+ ) Cofactor analogs –Warfarin Suicide substrates

Lecture 26 ATP and Phosphoryl Group Transfers

Phosphate Esters and Anhydrides

Phosphoryl Group Transfers

Phosphoryl (Not Phosphate) Transfers

Nucleophilic Displacements

ATP as a Phophoryl Donor 2 roles for ATP –Thermodynamic Drive unfavorable reactions –Mechanistic Offer 3 electrophilic phosphorous atoms for nucleophilic attack

ATP as Phosphoryl Donor 3 points of nucleophilic attack

Pyrophosphorylation: Attack on  -P

Phosphorylation: Attack on  -P

Amino Acid Sidechains as Nucleophiles

Enzymatic Phosphoryl Transfers Four classes –Phosphatases Water is acceptor/nucleophile –Phosphodiesterases Water is acceptor/nucleophile –Kinases Nucleophile is not water –Phosphorylases Phosphate is nucleophile

Phosphatases: Glucose-6- Phosphatase

Phosphatases: Glucose-6- Phosphate

Phosphodiesterases: RNAase

Kinases:  -Phosphoryl Transfer Transfer from ATP

Kinases: P-Enzyme Intermediates

Kinases

Pyruvate Kinase Makes ATP (∆Gº= –31 kJ/mol) from PEP ∆Gº= –62 kJ/mol

Phosphoryl-Group Transfer Potential

Significance of “High-Energy” P Compounds Drive synthesis of compounds below Phosphated compounds are more reactive –Thermodynamically –Kinetically If organism has ATP (etc…), it can do work and resist entropy  Cells must get ATP

Download ppt "Thermodynamics & ATP Review thermodynamics, energetics, chemical sense, and role of ATP."

Similar presentations