BIOENERGETICS

Biochemists study the chemistry of living systems in terms of chemical

composition, 3D structure, assembly of biological molecules, how life is
sustained and the degradation of biological molecules.
It is essential to understand how free energy is generated and how it is utilized
for cellular work.
Bioenergetics is the study of the energy and bio-matter transformations in
biosystems.
Bioenergetics is related to metabolism: the sum of all chemical reactions in an
organism.

CATABOLIC AND ANABOLIC REACTIONS

The free energy released in degradative
pathways is conserved by the synthesis of ATP
from ADP + Pi or by the reduction of the
coenzyme NAD(P)H. ATP and NAD(P)H are the
major sources of energy for anabolic reactions.

Bioenergetics is founded on the laws of thermodynamics, which considers the

physical theory of heat & energy distribution in the universe.

LAWS OF THERMODYNAMICS
1st law  energy can neither be created not destroyed but can be converted
from one form to another.
2nd law  spontaneous processes occur in directions that increase the overall
order.

Bioenergetics incorporates the energy changes associated with biomolecules

changing from one chemical form to another in metabolism.

BIOENERGETICS AND THERMODYNAMICS

Living organisms are dependent on catabolic reactions for energy production
and biomass synthesis. The relationship between energy & synthesis reactions
is critical in understanding the balance of inputs & outputs from the
biodegradation process.

METABOLISM
Metabolism is the process through which living systems acquire and use free
energy.
Catabolism (degradation)  nutrients and cell constituents are broken down
Anabolism (biosynthesis)  biomolecules are synthesized.

Catabolic reactions generally release free energy (exergonic). The free energy
released is used to driver anabolic reactions that require energy (endergonic),
perform mechanical work and actively transport biomolecules.

Exergonic and endergonic reactions are often coupled through the intermediate
synthesis of the high-energy compound ATP.

Metabolic pathways are irreversible. Every metabolic pathway has a first

committed step.
An exergonic, irreversible
reactions occurs early in the
pathway, commits the product to
continue.
As catabolic pathways differ, it allows
independent control over the 2
processes.

Diverse substances such as lipids,

proteins and carbohydrates
converge on a few common
intermediates. These
intermediates are further
metabolized in a central oxidative
pathway.
Complex metabolites are exergonically broken down into simpler products,
mainly to a common intermediate, acetyl-CoA.

Biosynthetic pathways carry out the opposite process. Relatively few

metabolites serve as starting materials for a host of varied products.

ENERGY IN METABOLIC REACTIONS

Gibbs Free Energy  energy produced or consumed by a chemical reaction, ∆G
(units: kJ.mol-1)

Spontaneous processes have a negative ∆G and are exergonic.

Non spontaneous processes have positive ∆G and are termed endergonic.
these processes are driven by the input of free energy.

COUPLED REACTIONS
The additivity of free energy changes allows an endergonic reaction to be
driven by an exergonic reaction. This is the thermodynamic basis for the
operation of metabolic pathways, as most reactions sequences comprise
endergonic & exergonic reactions.

Example:
1. A + B  C + D ∆G1
2. D + E  F + G ∆G2

if ∆G1 ≥ 0, the reaction will not occur spontaneously. however, if ∆G 2 is

sufficiently exergonic such that ∆G1 + ∆G2 < 0, then reaction 2 can drive
reaction 1.

If the overall pathway is exergonic, the reaction sequences will operate in a

forward direction.

BIOENERGETICS OF OXIDATION-REDUCTION REACTIONS

Most living organisms derive most of their free energy from oxidation-reduction
reactions.
In aerobic metabolism, free energy from the oxidation of carbohydrates is
harvested in the form of ATP.

Oxidation-reduction reactions involve group transfer; the groups transferred

are electrons, which are passed from electron donor (reductant or reducing
agent) to an electron acceptor (oxidant or oxidizing agent).

REDUCTION POTENTIAL (Ɛ)

The more positive the standard reduction potential, the higher the affinity of
the redox couple’s oxidized form for electrons.

The total standard reduction potential of any two half reactions is:

A positive ∆Eo is indicative of a spontaneous reaction, i.e. one that can-do work.

The total standard reduction potential is related to free energy by the following
equation:

number of electrons Faradays constant – 96.494

transferred kJ.V-1.mol-1. Faraday is the
electrical charge of 1 mol of
electrons.
EXAMPLE
Alcohol dehydrogenase catalyzed the oxidation of ethanol to acetaldehyde. From the
reduction potentials of the half reactions, calculate ∆Go’.

THERMODYNAIMCS OF PHOSPHATE COMPOUNDS

The most common cellular currency is adenosine triphosphate (ATP). ATP consists of
an adenosine to which 3 phosphoryl groups are linked via a phosphor-ester bond and
2 phospho-anhydride bonds.
ROLE OF ATP: Phosphoryl-Transfer Reactions
Of the most important phosphoryl-transfer reactions involve the synthesis and
hydrolysis of ATP.
ATP + H2O  ADP + Pi
ATP + H2O  AMP + PPi

ATP is regenerated by coupling its formation to a more highly exergonic metabolic

process.

ATP is regenerated by coupling its synthesis from ADP and P i to the even more
exergonic hydrolysis of phospho-enol pyruvate.

ATP has an intermediate phosphate group-transfer

potential. Highly exergonic phosphoryl-transfer
reactions of degradation are coupled to the
formation of ATP from ADP and Pi. Thus, ATP
serves as an energy conduit between ‘high
energy’ & ‘low energy’ phosphate acceptors.
Enzymes known as kinases catalyze the transfer of
phosphoryl groups between ATP and other
molecules.

In its role as a universal energy currency, ARP is

consumed:
1. In the early stages of nutrient breakdown (early stages of glycolysis).
2. Interconversion of nucleoside triphosphates (CTP, GTP & UTP), all these NTPs are
synthesized from ATP.
ATP + NDP  ADP + NTP
3. Physiological processes, e.g. protein folding, muscle contraction, transport of
molecules & ions against a concentration gradient.

In general, these processes occur from conformation changes in enzymes that occur
in response to binding ATP. This is followed by the exergonic hydrolysis of ATP and
release of ADP and Pi.

FORMATION OF ATP
1. Substrate level phosphorylation
occurs in early stages of carbohydrate metabolism
2. Oxidative phosphorylation & photo-phosphorylation
these processes generate a proton gradient. Discharge of the gradient is
enzymatically coupled to the formation of ATP.

RATE OF ATP TURNOVER

Typically, a cell only has an ATP supply sufficient to supply its energy needs for
approximately a minute (brain cells have only a few seconds supply). Hence, ATP is
continually being hydrolyzed and regenerated.
A person at rest consumes and regenerates ATP at a rate of roughly 3 mol (1.5 kg).h -1.
During exercise this amount increases by as much as an order of magnitude.

THE ∆GO’ OF HYDROLYSIS

Free energies of phosphate hydrolysis of biological compounds:
ORGANIC REACTION MECHANISMS
Almost all reactions that occur in metabolic pathways are enzymatically catalyzed
organic reactions.

CHEMICAL LOGIC
A covalent bond consists of an electron pair shared between 2 atoms. If the bond is
broken, the electron pair can:
remain with one of the atoms  Heterolytic cleavage
or separate such that one electron accompanies each of the atoms  Homolytic
cleavage.

Heterolytic C-H bond cleavage involves carbanion and proton formation:

Bond cleavage in which the electron pair remains with the carbon atom is
predominant in C-H bond breaking biochemistry. Hydride ion abstraction occurs only if
the hydride is transferred directly to an acceptor such as NAD +.

Homolytic bond cleavage produces unstable radicals, this occurs mostly in oxidation-
reduction reactions.

INTRODUCTION TO METABOLISM
Compounds participating in reactions involving heterolytic bond cleavage and
formation are categorized as electron rich or electron deficient.

Electrophiles
Nucleophiles

Nucleophiles are negatively charged or contain unshared electrons that easily form
covalent bonds with electron deficient centers.

BIOLOGICALLY IMPORTANT NUCLEOPHILIC GROUPS

The nucleophilic forms of these groups are their basic forms:
CHEMICAL LOGIC cont…
Electrophiles may be positively charges, contain an unfilled valence electron shell, or
contain an electronegative atom. The most common electrophiles in biochem are:

CURVED ARROW CONVENTION

Reactions are best understood if the electron pair rearrangements involved in going
from reactants to products are traced  use curved arrow convention.
i.e. The movement of an electron pair is symbolized by a curved arrow emanating
from the electron pair and pointing to the electron deficient center attracting the
electrons.

BIOCHEMICAL REACTIONS
Biochemical reactions can be classified into 4 categories:
- Group transfers
- Oxidation reductions
- Eliminations, isomerization’s & rearrangements
- reactions that make or break C-C bonds.

GROUP TRANSFERS
1. Acyl group transfer from one nucleophile to another:
 2. Phosphoryl group transfer of a nucleophile to a phosphoryl phosphorus atom,
e.g. the phosphoryl-transfer reaction catalyzed by hexokinase.

OXIDATION AND REDUCTIONS

Redox reactions involve the los or gain of
electrons. Many redox reactions in the metabolic
pathways involve C-H cleavage with the
ultimate loss of 2 electrons by the carbon atom.
These electrons are transferred to an electron
acceptor such as NAD+.
ELIMINATIONS
Eliminations result in the formation of a double
bond between two previously single bonded
saturated centers.
Substances eliminated may be H2O, NH3 or
alcohol (ROH).

e.g. from glycolysis, enzyme enolase, 2-

phosphoglycerate is dehydrated to
phosphoenolpyruvate (-H2O).

BIOCHEMICAL ISOMERIZATIONS
Biochemical isomerization’s involve the intra-molecular shift of a
hydrogen atom, which changes the location of the double bond.
A proton is removed from one carbon and added to another.
The most prevalent metabolic isomerization is the interconversion
of aldose  ketose.

e.g. from glycolysis, enzyme phosphoglucose isomerase, Glucose-

6-phosphate is converted to fructose-6-phosphate (isomerization
of an aldose to a ketose).

REACTIONS THAT MAKE AND BREAK C-C BONDS

These reactions form the basis of degradative and biosynthetic metabolism. The
breakdown of glucose to CO2 involves 5 cleavage reactions. The synthesis of glucose
involves the reverse process.