Lecture Connections 13 | Bioenergetics and Reactions

CHAPTER 13Bioenergetics and Reactions – Thermodynamics applies to biochemistry, too – Organic chemistry principles are still valid – Some biomolecules are “high energy” with respect to t

Lecture Connections

13 | Bioenergetics and Reactions

© 2009 W H Freeman and Company

CHAPTER 13

Bioenergetics and Reactions

– Thermodynamics applies to biochemistry, too – Organic chemistry principles are still valid

– Some biomolecules are “high energy” with

respect to their hydrolysis and group transfers – Energy stored in reduced organic compounds can be used to reduce cofactors such as NAD+

and FAD, which serve as universal electron

carriers

Key topics:

Life Needs Energy

• Recall that living organisms are built of complex

structures

• Building complex structures that are low in entropy

is only possible when energy is spent in the

process

• The ultimate source of this energy on Earth is the sunlight

Metabolism Is the Sum of All Chemical Reactions in the Cell

• Series of related reactions form metabolic pathways

• Some pathways are primarily energy-producing

Laws of Thermodynamics Apply

to Living Organisms

• Living organisms cannot create energy from nothing

• Living organisms cannot destroy energy into nothing

• Living organism may transform energy from one form to another

• In the process of transforming energy, living organisms

must increase the entropy of the universe

• In order to maintain organization within the themselves,

living systems must be able to extract useable energy from the surrounding, and release useless energy (heat) back

to the surrounding

Free Energy, or the Equilibrium Constant Measure the Direction

of Spontaneous Processes

Hydrolysis Reactions tend to be Strongly Favorable (Spontaneous)

Isomerization Reactions Have Smaller Free Energy Changes

• Isomerization between enantiomers: G = 0

Complete Oxidation of Reduced Compounds is Strongly Favorable

• This is how chemotrophs obtain most of their

energy

• In biochemistry the oxidation of reduced fuels

with O2 is stepwise and controlled

• Recall that being thermodynamically favorable

is not the same as being kinetically rapid

Lesson in Quantum Chemistry

• Most organic molecules, including the reduced fuels, are in the singlet spin state

– All electrons are paired into electron pairs

• Molecular oxygen is in the triplet spin state

– Two electrons are unpaired

• Direct electron transfer from a singlet reduced species to a triplet oxidizing species is quantum-mechanically forbidden

• This is why direct oxidation (spontaneous combustion) of biomolecules does not occur readily

• Few cofactors, such as transition metal ions, and flavin

adenine dinucleotide are able to catalyze consecutive

single-electron transfers needed for utilization of O2

Review of Organic Chemistry

• Most reactions in biochemistry are thermal

heterolytic processes

• Nucleophiles react with electrophiles

• Heterolytic bond breakage often gives rise to transferable groups, such as protons

• Oxidation of reduced fuels often occurs via

transfer of electrons and protons to a dedicated redox cofactors

Chemical ReactivityMost reactions fall within few categories:

• Oxidations-reductions (e - transfers)

• Group transfers (H + , CH3+ , PO32- )

• Cleavage and formation of C–C bonds

• Cleavage and formation of polar bonds

• Nucleophilic substitution mechanism

Group Transfer Reactions

• Proton transfer, very common

• Methyl transfer, various biosyntheses

• Acyl transfer, biosynthesis of fatty acids

• Glycosyl transfer, attachment of sugars

• Phosphoryl transfer, to activate metabolites,

also important in signal transduction

Chemistry at CarbonCovalent bonds can be broken in two ways

Homolytic cleavage is very rare, heterolytic cleavage

is common but does not occur for C-C bonds as

shown above

Nucleophiles and Electrophiles in

Biochemistry

Examples of Nucleophilic Carbon Bond Formation Reactions

Nucleophilic Displacement

• Substitution from sp3 phosphorous proceeds via the nucleophilic substitution (usually associative,

SN2-like) mechanism

– Nucleophile forms a partial bond to the

phosphorous center giving a pentacovalent

intermediate or a pentacoordinated transition state

Phosphoryl Transfer from ATP

• ATP is frequently the donor of the phosphate

in the biosynthesis of phosphate esters

Hydrolysis of ATP is Favorable

Under Standard Conditions

• Better charge separation in products

• Better solvation of products

• More favorable resonance stabilization of products

Actual  G of ATP Hydrolysis

Differs from  G’°

• The actual free energy change in a process depends on

– The standard free energy

– The actual concentrations of reactants and products

• The free energy change is more favorable if the reactant’s concentration exceeds its equilibrium concentration

• True reactant and the product are Mg-ATP and Mg-ADP, respectively

– G0 also Mg++ dependent

] MgATP [

] P [ ] MgADP [

Actual ATP Concentration Depends on Tissue Type

• Cellular ATP concentration is usually far above the equilibrium concentration, making ATP a very

potent source of chemical energy

Several Phosphorylated Compounds

Have Large  G’° for Hydrolysis

• Again, electrostatic repulsion within the reactant molecule is relieved

• The products are stabilized via resonance, or by more favorable solvation

• The product undergoes further tautomerization

Phosphates: Ranking by the

Standard Free Energy of Hydrolysis

• Reactions such as PEP + ADP = Pyruvate +

ATP

are favorable, and can be used to synthesize

ATP

Hydrolysis of Thioesters

• Hydrolysis of thioesters, such as acetyl-CoA is

strongly favorable

• Acetyl-CoA is an important donor of acyl groups

– Feeding two-carbon units into metabolic pathways

– Synthesis of fatty acids

• In acyl transfers, molecules other than water accept the acyl group

Molecular Basis for Thioester

Oxidation-Reduction Reactions

• Reduced organic compounds serve as fuels

from which electrons can be stripped off

during oxidation

Reversible Oxidation of a Secondary Alcohol to a Ketone

• Many biochemical oxidation-reduction

reactions involve transfer of two electrons

• In order to keep charges in balance, proton transfer often accompanies electron transfer

• In many dehydrogenases, the reaction

proceeds by a stepwise transfers of proton (

H+ ) and hydride ( :H- )

NAD and NADP are Common

• In a typical biological oxidation reaction, hydride

from an alcohol is transferred to NAD+ giving NADH

Formation of NADH can be Monitored by UV-Spectrophotometry

• Measure the change of absorbance a 340 nm

• Very useful signal when studying the of

kinetics of

NAD-dependent dehydrogenases

Flavin Cofactors allow Single

Electron Transfers

• Permits the use of molecular oxygen as an

ultimate electron acceptor

– flavin-dependent oxidases

• Flavin cofactors are tightly bound to proteins

Chapter 13: Summary

is much lower than the free energy of reactants In biochemical

phosphoryl transfer reactions, the good phosphate donors are

destabilized by electrostatic repulsion, and the reaction products are

often stabilized by resonance.

highly favorable reaction to the unfavorable reaction For example, ATP can be synthesized in the cell using energy in phosphoenolpyruvate.

reduced organic compounds to specialized redox cofactors The

reduced cofactors can be used in the biosynthesis, or may serve as a source of energy for ATP synthesis

In this chapter, we learned that the rules of thermodynamics, and organic chemistry still apply to living systems

For example: