CHAPTER 13
Bioenergetics and Reactions
Key topics:
– 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
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
– this is catabolism
• Some pathways are primarily using energy to build
complex structures
– this is anabolism or biosynthesis
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)
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 Reactivity
Most 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
• Addition–elimination mechanism
• Hydrolysis and condensation reactions
• Internal rearrangements
• Eliminations (without cleavage)
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
[ MgADP ]  [ Pi ]
G  G '  RT ln
[ MgAT P2 ]
0
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
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
Redox Cofactors
• These are commonly called pyridine
nucleotides
• They can dissociate from the enzyme after the
reaction
• 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