8 Energy, Enzymes, and

Metabolism
 ANALYSIS QUESTION: Be ready to provide the answer to the following at some point in Lecture

2. Which of the following reactions is most likely to

have a change in free energy similar to the one
shown?
a. Hydrolysis of ATP
b. Synthesis of sucrose from glucose and fructose
c. Synthesis of ATP from ADP and Pi
d. Formation of oxyluciferin from luciferin
e. Formation of glucose-6-phosphate from
glucose
1. Which of the following statements about the
reaction shown is true?
a. It is an endergonic reaction.
b. The reactants have less energy than the
products.
c. G is negative.
d. It is an example of a condensation reaction.
e. It is an anabolic reaction.
Learning Objectives:

• Apply the second law of thermodynamics to biological systems.

• Differentiate between exergonic and endergonic reactions.
• Explain the characteristics of ATP that account for the high free energy released during its
hydrolysis to form ADP and P¡.
• Analyze evidence to identify reactions as exergonic or endergonic. .
• Describe a catalyst.
• Describe how an enzyme-substrate complex form.
• Describe the relationship between an enzyme and the equilibrium point of the reaction it catalyzes
• Give examples of mechanisms for enzyme catalysis.
• Describe coenzymes and cofactors and how they function.
• Predict changes in the rate of an enzyme-catalyzed reaction as factors in the reaction are varied.
• Explain how metabolic pathways can shift in different directions.
• Apply the concept of allosteric regulation to explain experimental results.
Thermodynamics is a branch of
physics which deals with the energy
and work of a system. It was born in
the 19th century as scientists were
first discovering how to build and
operate steam engines.

The laws of thermodynamics apply to all

matter and all energy transformations in
the universe.
They help us to understand how cells
harvest and transform energy to sustain
life.
 All forms of energy are either:
Potential energy—energy stored as chemical bonds, concentration gradient, charge imbalance, etc.
Kinetic energy—the energy of movement.
Energy can be converted from one form to another.

Figure 8.1 Energy Conversions and Work A leaping frog illustrates both the
conversion between potential and kinetic energy
8.1 What Physical Principles Underlie Biological Energy Transformations?

Metabolism: the sum total of all chemical reactions occurring in a biological system at a given time.
Metabolic reactions involve energy changes.

Two types of metabolism:

• Anabolic reactions: complex molecules are made from simple molecules, and energy input is required.
Biosynthetic processes

• Catabolic reactions: complex molecules are broken down to simpler ones, and energy is released.
Degradative processes

Catabolic and anabolic reactions are often linked.

The energy released in catabolic reactions is used to drive anabolic reactions—to do biological work.
8.1 What Physical Principles Underlie Biological Energy Transformations?

First law of thermodynamics:

Analyze the diagram and state the first law of thermodynamics

8.1 What Physical Principles Underlie Biological Energy Transformations?

First law of thermodynamics:

Energy is neither created nor destroyed; but can be

transformed from one form to another.
8.1 What Physical Principles Underlie Biological Energy Transformations?
Second law of thermodynamics:

Analyze the diagram and state the second law of thermodynamics

8.1 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; some energy is lost to disorder.
With repeat transformations free energy is reduced and unusable energy (disorder) increases. A
phenomenon known as increase in enthropy.
Total energy = usable energy + unusable energy
H   =   G   +   TS

In biological systems, the total energy is called enthalpy (H).

The usable energy that can do work is called free energy (G). Free energy is what cells
require for all the chemical reactions involved in growth, cell division, and maintenance.
The unusable energy is represented by entropy (S) multiplied by the absolute
temperature (T).

Because we are interested in usable energy (free energy, G), we rearrange

Equation as : G   =   H   −   TS
The change in free energy (ΔG) of any
chemical reaction is equal to the
difference in free energy between the
products and the reactants:
ΔGreaction   =   Gproducts   −   Greactants

If a chemical reaction increases

entropy, the products will be more
disordered.
Example: In hydrolysis of a protein
into its component amino acids, ΔS
is positive.
Large changes in entropy make ΔG
more negative.
ΔG = ΔH – TΔS
8.1 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.
 ANALYSIS: Be ready to provide the answer to the following at some point in Lecture

1. Which of the following statements about the reaction shown is true?

a. It is an endergonic reaction.
b. The reactants have less energy than the products.
c. G is negative.
d. It is an example of a condensation reaction.
e. It is an anabolic reaction.
Learning Objectives:

• Explain the characteristics of ATP that account for the high free energy released during its
hydrolysis to form ADP and P¡.
• Analyze evidence to identify reactions as exergonic or endergonic. .
• Describe a catalyst.
• Describe how an enzyme-substrate complex form.
• Give examples of mechanisms for enzyme catalysis.
• Describe coenzymes and cofactors and how they function.
• Predict changes in the rate of an enzyme-catalyzed reaction as factors in the reaction are
varied.
• Explain how metabolic pathways can shift in different directions.
• Apply the concept of allosteric regulation to explain experimental results.
The formation of ATP is endergonic:
ADP + Pi + free energy  ATP + H2O

Formation and hydrolysis of ATP couples endergonic and exergonic reactions

ANALYSIS: Be ready to provide the answer to the following at some point in Lecture

2. Which of the following reactions is most likely to have

a change in free energy similar to the one shown?
a. Hydrolysis of ATP
b. Synthesis of sucrose from glucose and fructose
c. Synthesis of ATP from ADP and Pi
d. Formation of oxyluciferin from luciferin
e. Formation of glucose-6-phosphate from glucose
Learning Objectives:

• Describe a catalyst.
• Describe how an enzyme-substrate complex form.
• Give examples of mechanisms for enzyme catalysis.
• Describe coenzymes and cofactors and how they function.
• Predict changes in the rate of an enzyme-catalyzed reaction as factors in the reaction are varied.
• Explain how metabolic pathways can shift in different directions.
• Apply the concept of allosteric regulation to explain experimental results.
Describe catalyst(s)

Catalysts speed up the rate of a

reaction.
The catalyst is not altered by the
reactions.
Do you recall any
Most biological catalysts are other type of
enzymes (proteins) that act as a biological catalyst?
framework in which reactions
can take place. ANSWER:
RIBOZYMES
 Enzymes lower the energy barrier by bringing the reactants together.
They offer reactions an easier path, speeding them up.
Activation energy changes the reactants into unstable forms with higher free energy
—transition state intermediates
Enzymes are much larger than their substrates and the active site is usually small.
The shape of the active site allows a specific substrate to fit precisely.
ANALYZE

Trypsin and elastase are both enzymes that catalyze

hydrolysis of peptide bonds. But trypsin only cuts next to
lysine and elastase only cuts next to alanine. Why?
a. Trypsin is a protein, and elastase is not.
b. G for the two reactions is different.
c. The shape of the active site for the two enzymes is
different.
d. One of the reactions is endergonic, and the other is
exergonic.
e. Hydrolysis of lysine bonds requires water; hydrolysis of
alanine bonds does not.
Learning Objectives:

• Give examples of mechanisms for enzyme catalysis.

• Describe coenzymes and cofactors and how they function.
• Predict changes in the rate of an enzyme-catalyzed reaction as factors in the reaction are varied.
• Explain how metabolic pathways can shift in different directions.
• Apply the concept of allosteric regulation to explain experimental results.
In catalyzing a reaction, an enzyme
may use one or more mechanisms:
1. Orienting substrates
2. Inducing strain in substrates
3. Temporarily adding chemical groups
Acid–base catalysis: enzyme side chains transfer H+ to or from
the substrate, causing a covalent bond to break.
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.
Learning Objectives:

• Describe coenzymes and cofactors and how they function.

• Predict changes in the rate of an enzyme-catalyzed reaction as factors in the
reaction are varied.
• Explain how metabolic pathways can shift in different directions.
• Apply the concept of allosteric regulation to explain experimental results.
Table 8.2

Some enzymes require

“partners”:
• Prosthetic groups:
non-amino acid
groups bound
permanently to
enzymes
• Inorganic cofactors:
ions permanently
bound to enzyme
• Coenzymes: small
carbon-containing
molecules; not
permanently bound
Learning Objectives:

• Predict changes in the rate of an enzyme-catalyzed reaction as factors in the reaction are
varied.
• Explain how metabolic pathways can shift in different directions.
• Apply the concept of allosteric regulation to explain experimental results.
ANALYZE : EXPLAIN THE FOLLOWING GRAPH
Figure 8.13 Catalyzed Reactions Reach a Maximum Rate

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; it
is working at maximum
rate.

Figure 8.13 Catalyzed Reactions Reach a Maximum Rate Because there is usually
less enzyme than substrate present, the reaction rate levels off when the enzyme
becomes saturated.
Figure 8.19 pH Affects Enzyme Activity An enzyme catalyzes its reaction at a
maximum rate. The activity curve for each enzyme peaks at its optimal pH. For
example, pepsin is active in the acidic environment of the stomach, whereas
chymotrypsin is active in the small intestine.
Every enzyme is most active at a particular 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; this affects folding and thus
enzyme function.
Figure 8.20 Temperature Affects Enzyme Activity Each enzyme is most
active at a particular optimal temperature. At higher temperatures the
enzyme becomes denatured and inactive; this explains why the activity
curve falls off abruptly at temperatures above the optimum.
Every enzyme has an optimal temperature.
At high temperatures, noncovalent bonds begin to break.
Enzymes can lose tertiary structure and become denatured
Learning Objectives:

• Explain how metabolic pathways can shift in different directions.

• Apply the concept of allosteric regulation to explain experimental results.
8.5 How Are Enzyme Activities Regulated?

The thousands of chemical reactions

occurring in cells are organized in
metabolic pathways. Each reaction is
catalyzed by a specific enzyme.
The pathways are interconnected.
Regulation of enzymes and thus reaction
rates helps maintain internal
homeostasis.

Figure 8.14 Metabolic Pathways The complex interactions of metabolic pathways can be
modeled by the tools of systems biology. In cells, the main elements controlling these
pathways are enzymes.
The amount of enzyme activity in a cell is controlled
in two ways:
1.Regulation of gene expression
2.Regulation of enzyme activity
8.5 How Are Enzyme Activities Regulated?

Enzymes can be regulated by inhibitors

Inhibitors: molecules that bind to the enzyme and
slow reaction rates.
• Can occur naturally in a cell- regulate metabolism.
• Can be artificial- used to treat diseases, kill pests, to
study how enzymes work.
• Enzyme inhibitors can be
reversible or irreversible.
• Reversible inhibition: the
inhibitor can separate from the
enzyme, allowing the enzyme to
function fully as before.
Example; inhibitor bonds
noncovalently to the active site
and prevents substrate from
binding.
• Irreversible inhibition: enzyme
becomes permanently
inactivated. Example; inhibitor
covalently bonds to side
chains in the active
Figure 8.18 Feedback Inhibition of Metabolic Pathways

Metabolic pathways:

•The first reaction is the commitment step—other

reactions then happen in sequence.

•Feedback inhibition (end-product inhibition): the

final product acts as a noncompetitive inhibitor of
the first enzyme, which shuts down the pathway . https://www.quia.com/files/quia/users/lmcgee/Energy_Enzymes/feedback-inhibition.gif

Feedback inhibition
https://www.mirror.co.uk/news/world-news/horrific-nerve-gas-attack-syria-10161569
Figure 8.15 Irreversible Inhibition

Example: Irreversible Inhibition :

(Diisopropyl fluorophosphate)--
DIPF or nerve gas

https://peaknootropics.com/wp-content/uploads/2013/08/acetylcholine-metabolism.png
ANALYZE the following and explain what you think is happening. Would this most likely be a competitive, uncompetitive or non-
competitive inhibition?

FOLIC ACID
x
Learning Objectives:

• Apply the concept of allosteric regulation to explain experimental results.

Figure 8.17 Allosteric Regulation of Enzymes

Allosteric regulation: an effector

(Inhibitors and activators) binds
enzyme at a site different from the
active site, which changes its shape.
Active form of enzyme—can bind
substrate.
Inactive form of enzyme —cannot bind
substrate but can bind an inhibitor.

Most allosteric enzymes are proteins

with quaternary structure.

The active site is on the catalytic

subunit.

Inhibitors and activators bind to other

polypeptides called regulatory
subunits.
8.5 How Are Enzyme Activities Regulated?

Some allosteric enzymes have multiple

subunits with active sites. Substrate binding
at one site can have allosteric effects, and
reaction rate increases.

Reaction rates versus substrate concentration

are very different for these types of allosteric
enzymes compared to single subunit Allosteric enzyme having have multiple catalytic
subunits with active sites.
enzymes.
In-Text Art, Ch. 8, p. 159 (1)

Allosteric enzyme having have

single catalytic subunit enzyme multiple catalytic subunits with
active sites.
8.5 How Are Enzyme Activities Regulated?

Many enzymes are regulated through reversible

phosphorylation.
Enzymes can be activated when protein kinase adds
a phosphate group and deactivated by protein
phosphatase (remove phosphate groups).
ANALYZE

Which of the following statements best explains the shape of this curve?
a. The enzyme has multiple active sites. As the enzyme binds substrate at one site, it increases affinity for binding substrate at other active
sites.
b. The enzyme has a single active site. As the enzyme binds substrate, the activity of the enzyme stalls until it can clear the active site.
c. The enzyme has multiple active sites. As the substrate concentration increases, all sites must be equally bound for the reaction to proceed.
d. The enzyme has multiple active sites. Substrate binding at each of the sites is dependent upon the temperature of the reaction.
e. The enzyme has a single active site. Substrate binding at this particular site occurs within a narrow pH range, termed the equivalence point.
Do you Understand?

How do competitive and noncompetitive enzyme inhibitors differ from

each other?
a. Competitive inhibitors bind to the active site, whereas noncompetitive
inhibitors change the shape of the active site.
b. Competitive inhibitors have a higher energy of activation than
noncompetitive inhibitors have.
c. They function at different pH values.
d. Noncompetitive enzyme inhibitors contain magnesium, whereas
competitive inhibitors contain iron.
e. Noncompetitive enzyme inhibitors are reversible, whereas competitive
inhibitors are irreversible.
ANALYZE

Refer to the diagram below showing a metabolic pathway. Reactants and products are designated by
capital letters; enzymes are designated by numbers.

8. If end product E allosterically inhibits enzyme 1, a buildup of E in the cell will result in _______
production of _______.
a. reduced; G
b. reduced; A
c. increased; G
d. increased; E
e. increased; D
Analyze

Firefly bioluminescence occurs through the reaction of luciferin with luciferase. Attempting to impress
your friend, you find these reagents in the lab, mix them together, and no bioluminescence occurs. What
other reagent in the laboratory could you add to generate light and therefore impress your friends?
a. Purified AMP
b. Add more purified luciferase
c. Add oxyluciferin
d. Hold the test tube under a strong light source
e. Purified ATP