Bioenergetics: The Role of ATP and

Biologic Oxidation
Bioenergetics:
• The study of energy changes accompanying
biochemical reactions.
• The study of sources of energy in living organisms and
how that energy is ultimately utilized
• For any physical activity, energy must be generated
and used by the body to accomplish the task
Bioenergetics
• Each formation or breakdown of a
biomolelcule involves an associated energy
change.
• Thermodynamics is the field of chemistry
that studies these energy changes.
• Goal of thermodynamics is to predict
whether a reaction will occur spontaneously
which, in a chemical sense, means it will
continue without energy input once started.

4-3
Gibbs change in free energy ( G)
• Portion of the total energy change that is
available for doing work.
• Useful energy– chemical potential
General Laws of Thermodynamics
First Law: states that the total energy of a
system, including its surroundings, remains
constant.
CHANGE

Energy is neither lost nor gained

Transferred to another system

Transformed into another form of energy

Second Law: the total entropy of a system must
increase if a process is to occur
spontaneously.

Entropy: the extent of disorder or randomness

of the system and becomes maximum as
equilibrium is approached.
G G G G

= = = =

G
H
G =H H-T S equal to H G = E-T H S
- - - -
=T T T T

H
S
G Negative:
S S S
-
T •Reaction proceeds
S spontaneously with loss of free
energy.
•Exergonic (catabolism)
•Reaction reaches completion:
Irreversible
G

H
G:Positive
-
T •Reaction proceeds only if free
S energy can be gained.
•Endergonic (anabolism)
• Magnitude is great: system is
stable
• No tendency for a reaction to
occur
G

H
G:zero
-
T •System at equilibrium
S • No net change
Gibb’s Free Energy
• In a spontaneous reaction:
-free energy decreases, ΔG is negative
-energy is released by the reaction
-reaction is said to be exergonic
• In a non spontaneous reaction:
-free energy increases, ΔG is positive
-energy is absorbed by the reaction
-reaction is said to be endergonic

4-10
Coupled reactions:
- pairs of biochemical reactions that occur
concurrently in which energy released by one
reaction is used in the other reaction
 A
Heat
D

Chemical
energy

C B
A+C B + D + Heat
Coupling of an exergonic to an endergonic reaction
 A
D

B C

Transfer of free energy from an exergonic to an

endergonic reaction via a high-energy
intermediate compound
 METABOLISM

The sum total of all the biochemical

reactions that take place in a living
organism
 CATABOLISM
All metabolic reactions in
which large biochemical
molecules are broken
down to smaller ones
• Release energy

ANABOLISM
All metabolic reactions in
which small biochemical
molecules are joined
together to form larger
ones
• Requires energy
 ADENOSINE PHOSPHATES
(ATP, ADP, AMP)

AMP: nucleotides present in RNA molecules

ADP, ATP: differ structurally from AMP in the
number of phosphate groups present
ATP: phosphodiester bond joins the 1st phosphoryl
group to the pentose sugar ribose; other 2 are
joined by phosphoanhydride bonds

Phosphoryl group: functional group derived from a

phosphate ion that is a part of another molecule
ATP: 3 phosphoryl groups
ADP: 2 phosphoryl groups
AMP: 1 phosphoryl group
 When 2 phosphate groups react with one
another: water molecule is produced
(anhydride)

Phosphoanhydride bond: chemical bond

formed when 2 phosphate groups react with
each other and a water molecule is produced
ATP, ADP: readily undergo hydrolysis reactions in which
phosphate groups (Pi, inorganic phosphate) is released

Hydrolysis: energy producing reactions used to drive

cellular processes that require energy input
Phoshphoanhydride bonds in ATP and ADP very reactive
bonds that require less energy than normal to break

Reactive bonds called Strained bonds: basis for net energy

production that accompanies hydrolysis
 Greater than normal electron-electron repulsive forces at
specific locations within a molecule:
cause for bond strain

In ATP, ADP: it is the highly electronegative oxygen atoms in

the additional phosphate groups that cause the increased
repulsive strain
 Conversion Of Glucose To Glucose Phosphate:
1st step in glycolysis: reaction where ATP functions are both
a source of phosphate group and a source of energy

Uridine triphosphate (UTP): in carbohydrate metabolism

Guanosine triphosphate (GTP): in protein and carbohydrate
metabolism
Cytidine triphosphate (CTP): in lipid metabolism
 High Energy Phosphates
ATP: Donor of high energy phosphates
ADP: Accept high energy phosphates

Serve as energy currency of the cell.

Three Major Sources of Phosphates

1. Oxidative phosphorylation
- the greatest source
2. Glycolysis
- Two phosphates formed from one
molecule of glucose
3. Citric acid cycle
- One phosphate at the succinate
thiokinase step.
 Biologic Oxidation
Oxidation: removal /loss of electrons
Reduction: gain of electrons

• The free energy change is proportionate to the

tendency of reactants to donate or accept
electrons
• Enzymes: oxidoreductases
• Four groups: oxidases, dehydrogenases,
hydroperoxidases, oxygenases
Oxidation of an iron atom involves loss of an electron
(to an acceptor): Fe++ (reduced) à Fe+++ (oxidized) + e-
Since electrons in a C-O bond are associated more with O,
increased oxidation of a C atom means increased number
of C-O bonds.

H H O O O

H C H H C OH C C C
H H H OH
H H O

Increasing oxidation of carbon

Oxidation of carbon is spontaneous (energy-yielding).

Two important e- carriers in metabolism: NAD+ & FAD.
 1. OXIDASES: Use Oxygen as a Hydrogen
Acceptor
• Cytochrome oxidase
- hemoprotein
- contain heme prosthetic group
- cytochrome aa3
- terminal component of the respiratory
chain with oxygen as the hydrogen
acceptor
- inhibited by CO, cyanide, hydrogen
sulfide
- contain 2 molecules of heme and 2
molecules of Cu
FLAVIN ADENINE DINUCLEOTIDE (FAD, FADH2)

• Coenzyme required in numerous metabolic redox

reactions
• Block diagram of FAD from the three-subunit
viewpoint
FLAVIN ADENINE DINUCLEOTIDE (FAD, FADH2)

• Flavin and ribitol, the two components attached to the

ADP unit, together constitute the B vitamin riboflavin

• Ribitol: a reduced form of

ribose; a -CH2OH group is
present in place of the -CHO
group
• The active portion of FAD in metabolic redox reactions is
the flavin subunit of the molecule
• The flavin is reduced, converting the FAD to FADH2, a
molecule with two additional hydrogen atoms. Thus FAD is
the oxidized form of the molecule, and FADH2 is the
reduced form.
• A typical cellular reaction in which FAD serves as the
oxidizing agent involves a -CH2-CH2- portion of a
substrate being oxidized to produce a carbon–carbon
double bond.

• For an enzyme-catalyzed redox reaction involving

removal of two hydrogen atoms, such as this, each
removed hydrogen atom is equivalent to a hydrogen ion,
H+, plus an electron, e-.
• On the basis of this equivalency, the summary equation
relating the oxidized and reduced forms of flavin adenine
dinucleotide is usually written as
 2. DEHYDROGENASES: CANNOT USE OXYGEN
AS HYDROGEN ACCEPTOR

1. Transfer of hydrogen from one substrate to

another in a coupled redox reaction.
- use NAD/NADP as coenzyme
- reactions are reversible
- enables one substrate to be oxidized at the
expense of another
2. Transfer electrons in the respiratory chain of
electron transport from substrate to oxygen
 NICOTINAMIDE ADENINE DINUCLEOTIDE
(NAD, NADH)
• Parallels between NAD and FAD
– Both have coenzyme functions in metabolic
redox pathways,
– Both have a B vitamin (niacin) as a structural
component, and
• Detailed structure of NAD
reveals the basis for the
positive electrical charge
• + sign: positive charge on
the nitrogen atom in the
nicotinamide component
of the structure ( nitrogen
atom has four bonds
instead of usual three)
• Active portion of NAD+ in
metabolic redox
reactions: nicotinamide
subunit of the molecule
• The nicotinamide is reduced, converting the NAD+
to NADH, a molecule with one additional hydrogen
atom and two additional electrons.
• Thus NAD+ is the oxidized form of the molecule,
and NADH is the reduced form
• A typical cellular reaction in which NAD+ serves as
the oxidizing agent is the oxidation of a secondary
alcohol to give a ketone.
• One hydrogen atom of the alcohol substrate is
directly transferred to NAD+
• The other appears in solution as H+ ion.
• Both electrons lost by the alcohol go to the
nicotinamide ring in NADH. (Two electrons are
required, rather than one, because of the original
positive charge on NAD+)
• Summary equation relating the oxidized and
reduced forms of nicotinamide adenine
dinucleotide
DEHYDROGENASES

NAD-linked dehydrogenases
• Glycolysis
• Citric acid cycle
• Respiratory chain
NADP-linked dehydrogenases
• Pentose phosphate pathway
• steroid synthesis
• Extramitochondrial of fatty acid synthesis
DEHYDROGENASES

Riboflavin-liked dehydrogenases
- electron transport in respiratory chain
NADH dehydrogenase
- carrier of electrons
Cytochromes
- carriers of electrons
3. HYDROPEROXIDASE: Use Hydrogen
peroxide or an organic peroxide as
substrate
• Protect the body against peroxides
• Peroxidases and catalase

Peroxidases
• Contain protoheme as prosthetic group
• Electron acceptor: ascorbate, quinines, cytochrome c
• Eg. Glutathione peroxidase

PEROXIDASE
H2O2 + AH2 2H2O + A
Catalase
- hemoprotein with four heme groups
- use one molecule of H2O2 as electron acceptor
and another molecule as electron donor.
- destroy hydrogen peroxide formed by the action
of oxidases.

CATALASE
2H2O2 2H2O2 + O2
 4. OXYGENASES
• Synthesis or degradation of metabolites
• Catalyze incorporation of oxygen into a
substrate molecule in two steps
1. oxygen is bound to the enzyme at the
active site
2. the bound oxygen is reduced or
transferred to the substrate.
A. Dioxygenase
- incorporate both atoms of the molecular
oxygen into the substrate

A + O2 AO2
B. Monooxygenases
- Incorporate only one atom of a
molecular oxygen into the substrate
- cytochrome P450

A –H + O2 + ZH2 A-OH +H2O + Z

Cytochrome P450
-heme containing monooxygenase
- located in the ER (liver and intestine)
and mitochondria
- together with cytochrome b5: Major role
in drug metabolism and detoxification
- rate of detoxification by cytochrome
P450: determines the duration of their
action
Mitochondrial cytochrome P450
- found in steroidogenic tissues
- concerned with biosynthesis of steroid
hormones
 SUPEROXIDE DISMUTASE
• Remove superoxide anion free radical
• Superoxide anion free radical (O2-): formed from
the transfer of a single electron to O2

Enz – Flavin – H2 + O2 Enz – Flavin – H +O2- + H-