6
Energy, Enzymes, and
Metabolism
6 Energy, Enzymes, and Metabolism
• 6.1 What Physical Principles Underlie
Biological Energy Transformations?
• 6.2 What Is the Role of ATP in
Biochemical Energetics?
• 6.3 What Are Enzymes?
• 6.4 How Do Enzymes Work?
• 6.5 How Are Enzyme Activities Regulated?
6.1 What Physical Principles Underlie Biological Energy
Transformations?
The transformation of energy is a
hallmark of life.
Energy is the capacity to do work, or the
capacity to change.
Energy transformations are linked to
chemical transformations in cells.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
All forms of energy can be placed in two
categories:
• Potential energy is stored energy—as
chemical bonds, concentration gradient,
charge imbalance, etc.
• Kinetic energy is the energy of
movement.
Energy Conversions and Work
Potential E = 100%
Potential E = 50%
Figure 6.1 Energy Conversions and Work
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Metabolism: sum total of all chemical
reactions in an organism
Anabolic reactions: complex molecules
are made from simple molecules; energy
input is required.
Catabolic reactions: complex molecules
are broken down to simpler ones and
energy is released.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
First Law of Thermodynamics: Energy
is neither created nor destroyed.
When energy is converted from one form
to another, the total energy before and
after the conversion is the same.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Second Law of Thermodynamics:
When energy is converted from one
form to another, some of that energy
becomes unavailable to do work.
No energy transformation is 100 percent
efficient.
Figure 6.2 The Laws of Thermodynamics
6.1 What Physical Principles Underlie Biological Energy
Transformations?
In any system:
total energy = usable energy + unusable energy
Enthalpy (H) = Free Energy (G) + Entropy (S)
or H = G + TS (T = absolute temperature)
G = H – TS
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Change in energy can be measured in
calories or joules.
Change in free energy (ΔG) in a reaction
is the difference in free energy of the
products and the reactants.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
ΔG = ΔH – TΔS
If ΔG is negative, free energy is released.
If ΔG is positive, free energy is consumed.
If free energy is not available, the
reaction does not occur.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Magnitude of ΔG depends on:
ΔH—total energy added (ΔH > 0) or
released (ΔH < 0).
ΔS—change in entropy. Large changes in
entropy make ΔG more negative.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
If a chemical reaction increases entropy,
the products will be more disordered.
Example: hydrolysis of a protein into its
component amino acids—ΔS is positive.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Second Law of Thermodynamics:
Disorder tends to increase because of
energy transformations.
Living organisms must have a constant
supply of energy to maintain order.
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Exergonic reactions release free energy
(–ΔG)—catabolism
Endergonic reactions consume free
energy (+ΔG)—anabolism
Figure 6.3 Exergonic and Endergonic Reactions
6.1 What Physical Principles Underlie Biological Energy
Transformations?
In principle, chemical reactions can run in
both directions.
Chemical equilibrium ΔG = 0
Forward and reverse reactions are
balanced.
AB
Figure 6.4 Chemical Reactions Run to Equilibrium
6.1 What Physical Principles Underlie Biological Energy
Transformations?
Every reaction has a specific equilibrium
point.
ΔG is related to the point of equilibrium:
the further towards completion the point
of equilibrium is, the more free energy is
released.
ΔG values near zero—characteristic of
readily reversible reactions.
6.2 What Is the Role of ATP in Biochemical Energetics?
ATP (adenosine triphosphate) captures
and transfers free energy.
ATP releases a large amount of energy
when hydrolyzed.
ATP can phosphorylate, or donate
phosphate groups to other molecules.
6.2 What Is the Role of ATP in Biochemical Energetics?
ATP is a nucleotide.
Hydrolysis of ATP yields free energy.
ATP  H 2O  ADP  Pi  free energy
ΔG = –7.3 kcal/mole
Figure 6.5 ATP (A)
6.2 What Is the Role of ATP in Biochemical Energetics?
Bioluminescence—an endergonic
reaction
luciferin  O2  ATP luciferase

 oxyluciferin  AMP  PPi  light
Figure 6.5 ATP (B)
Figure 6.6 Coupling of Reactions
Exergonic and endergonic reactions are coupled.
Figure 6.7 Coupling of ATP Hydrolysis to an Endergonic Reaction
6.3 What Are Enzymes?
Catalysts speed up the rate of a reaction.
The catalyst is not altered by the
reactions.
Most biological catalysts are enzymes
(proteins) that act as a framework in
which reactions can take place.
6.3 What Are Enzymes?
Some reactions are slow because of an
energy barrier = the amount of energy
required to start the reaction—
activation energy (Ea)
Figure 6.8 Activation Energy Initiates Reactions
6.3 What Are Enzymes?
Activation energy changes the reactants
into unstable forms with higher free
energy—transition state species.
Activation energy can come from heating
the system—the reactants have more
kinetic energy.
Enzymes lower the energy barrier by
bringing the reactants together.
6.3 What Are Enzymes?
Biological catalysts (enzymes and
ribozymes) are highly specific.
Reactants are called substrates.
Substrate molecules bind to the active
site of the enzyme.
Three-dimensional shape of the enzyme
determines the specificity.
Figure 6.9 Enzyme and Substrate
6.3 What Are Enzymes?
The enzyme-substrate complex is held
together by hydrogen bonds, electrical
attraction, or covalent bonds.
E + S → ES → E + P
The enzyme may change when bound to
the substrate, but returns to its original
form.
6.3 What Are Enzymes?
Enzymes lower the energy barrier for
reactions.
The final equilibrium doesn’t change, ΔG
doesn’t change.
Figure 6.10 Enzymes Lower the Energy Barrier
Figure 6.11 Life at the Active Site (A)
Enzymes orient substrate molecules, bringing
together the atoms that will bond.
Figure 6.11 Life at the Active Site (B)
Enzymes can stretch the bonds in substrate
molecules, making them unstable.
Figure 6.11 Life at the Active Site (C)
Enzymes can temporarily add chemical
groups to substrates.
6.4 How Do Enzymes Work?
Acid-base catalysis: enzyme side chains
transfer H+ to or from the substrate—a
covalent bond breaks
Covalent catalysis: a functional group in a
side chain bonds covalently with the
substrate
Metal ion catalysis: metals on side chains
loose or gain electrons
6.4 How Do Enzymes Work?
Shape of enzyme active site allows a
specific substrate to fit—the “lock and
key.”
Many enzymes change shape when they
bind to the substrate—induced fit.
Figure 6.12 Some Enzymes Change Shape When Substrate Binds to Them
6.4 How Do Enzymes Work?
Some enzymes require “partners”:
• Prosthetic groups: non-amino acid
groups bound to enzymes
• Cofactors: inorganic ions
• Coenzymes: not bound permanently to
enzymes
Figure 6.13 An Enzyme with a Coenzyme
6.4 How Do Enzymes Work?
The rate of a catalyzed reaction depends
on substrate concentration.
Concentration of an enzyme is usually
much lower than concentration of a
substrate.
At saturation, all enzyme is bound to
substrate—maximum rate.
Figure 6.14 Catalyzed Reactions Reach a Maximum Rate
6.4 How Do Enzymes Work?
Rate can be used to calculate enzyme
efficiency: molecules of substrate
converted to product per unit time—also
called turnover.
Ranges from 1 to 40 million molecules
per second!
6.5 How Are Enzyme Activities Regulated?
Thousands of chemical reactions are occurring
in cells simultaneously.
The reactions are organized in metabolic
pathways. Each reaction is catalyzed by a
specific enzyme.
The pathways are interconnected.
Regulation of enzymes and thus the rates of
reactions helps maintain internal homeostasis.
6.5 How Are Enzyme Activities Regulated?
Metabolic pathways can be modeled
using mathematical algorithms.
This new field is called systems biology.
Figure 6.15 Metabolic Pathways
6.5 How Are Enzyme Activities Regulated?
Inhibitors regulate enzymes: a molecule
that binds to the enzyme and slows
reaction rates.
Naturally occurring inhibitors regulate
metabolism.
6.5 How Are Enzyme Activities Regulated?
Irreversible inhibition: inhibitor
covalently bonds to side chains in the
active site—permanently inactivates the
enzyme.
Example: DIPF or nerve gas
Figure 6.16 Irreversible Inhibition
6.5 How Are Enzyme Activities Regulated?
Reversible inhibition: inhibitor bonds
noncovalently to the active site,
prevents substrate from binding—
competitive inhibitors.
When concentration of competitive
inhibitor is reduced, it detaches from the
active site.
Figure 6.17 Reversible Inhibition (A)
6.5 How Are Enzyme Activities Regulated?
Noncompetitive inhibitors: bind to the
enzyme at a different site (not the active
site).
The enzyme changes shape and alters
the active site.
Figure 6.17 Reversible Inhibition (B)
6.5 How Are Enzyme Activities Regulated?
Allostery (allo, “different”; stery, “shape”)
Some enzymes exist in more than one
shape:
• Active form—can bind substrate
• Inactive form—cannot bind substrate but
can bind an inhibition
6.5 How Are Enzyme Activities Regulated?
Most allosteric enzymes are proteins with
quaternary structure.
Active site is on one subunit, the
catalytic subunit
Inhibitors and activators bind to the
regulatory subunits
Figure 6.18 Allosteric Regulation of Enzymes
Figure 6.19 Allostery and Reaction Rate
(Sigmoid or S-shaped plot)
6.5 How Are Enzyme Activities Regulated?
Metabolic pathways:
The first reaction is the commitment
step—other reactions then happen in
sequence.
The final product may allosterically inhibit
the enzyme needed for the commitment
step, which shuts down the pathway—
feedback inhibition or end-product
inhibition.
Figure 6.20 Feedback Inhibition of Metabolic Pathways
6.5 How Are Enzyme Activities Regulated?
Every enzyme has an optimal pH.
pH influences the ionization of functional
groups.
Example: at low pH (high H+) —COO–
may react with H+ to form —COOH
which is no longer charged—affects
folding and thus enzyme function.
Figure 6.21 pH Affects Enzyme Activity
6.5 How Are Enzyme Activities Regulated?
Every enzyme has an optimal
temperature.
At high temperatures, noncovalent bonds
begin to break.
Enzyme can lose its tertiary structure and
become denatured.
Figure 6.22 Temperature Affects Enzyme Activity
6.5 How Are Enzyme Activities Regulated?
Isozymes: enzymes that catalyze the
same reaction but have different
properties, such as optimal temperature.
Organisms can use isozymes to adjust to
temperature changes.
Enzymes in humans have higher optimal
temperature than enzymes in most
bacteria—a fever can denature the
bacterial enzymes.