Cells and Cellular Processes:

An overview of cellular metabolism

Classification of Organisms based on Carbon and Energy Utilization

Cellular Metabolism is Organized into Pathways

The living cell is a miniature factory where

thousands of reactions occur

The sum total of all the chemical conversions in a

cell is called metabolism.

Metabolism is organized into sequences of enzyme-

catalyzed chemical reactions called pathways.

All Metabolic pathways

are interconnected in a
complex set of
networks.
Intermediates of one
pathway may be
channeled into a
different pathway.
End products of a
pathway can also
regulate the enzymes at
the start point of the
same pathway.

Organization of the Chemistry of Life into

Metabolic Pathways

A metabolic pathway has many steps

That begin with a specific molecule and end with

a product
That are each catalyzed by a specific enzyme
Enzyme 1
A

Enzyme 3
D

B
Reaction 1

Starting
molecule

Enzyme 2

Reaction 2

Reaction 3
Product

Energy in Metabolism

Energy is either consumed or released

during the metabolic reactions.

Two types of energy (Kinetic and Potential

energy).

The laws of Energy is governed by the

laws of thermodynamics.

In living systems free energy is essential

for cellular work.

Exergonic and Endergonic Reactions in Metabolism

An exergonic reaction proceeds with a net release of free
energy and is spontaneous
An endergonic reaction absorbs free energy from its
surroundings and is non-spontaneous

Reactants

Amount of
Energy released
(G <0)
Energy

Products

Free energy

Free energy

Products

Energy

Amount of
energy
released
(G>0)

Reactants

Progress of the reaction

Progress of the reaction
(a) Exergonic reaction: energy released

(b) Endergonic reaction: energy required

Metabolism can be divided into two types of activities:

Anabolic and Catabolic reactions

Anabolic reactions are those that link simple molecules together

to make complex ones. These are endergonic reactions.

Catabolic reactions are those that break down complex

molecules into simpler ones. Catabolism is exergonic and
provides the energy for anabolic reactions.

Fats, a variety of sugars, and proteins can be consumed for

energy. All organisms use glucose as a primary fuel molecule.

Energy released from catabolism may be stored in chemical

bonds, reduced co-enzymes or ion gradients.

Food is Broken into Metabolic Intermediates with release of Energy

Cellular metabolism is subject to the

Laws of Thermodynamics !
Living organisms extract energy from their
environment and convert some of it into
useful forms of energy to produce work.
During metabolic transductions, the total
entropy increases as the enthalpy of the
nutrients decrease.
Part of the increase in entropy is in the form
of heat dissipation, and part of it due
increase in chemical entropy of endproducts.
One effect of these transformations is
increased order (lower entropy) in the form
of complex macromolecules and cellular
structures.

Biological Order and Disorder

Living systems
Increase the entropy of the universe
Use energy to maintain order
50m

Figure 8.4
11

Glucose Metabolism is highly Exergonic and coupled

to Production of NADH and ATP

The energy in glucose is contained in the reduced hydrocarbon bonds. The

metabolism of glucose is highly exergonic. To capture this energy, glucose must

be oxidized. Redox reactions transfer electrons and energy.

The coenzyme NAD (nicotinamide adenine dinucleotide) is a key electron

carrier in cellular redox reactions. NAD exists in an oxidized form, NAD+, and a
reduced form, NADH.

NADH + H+ + 1/2 O2 NAD+ + H2O. The G of this rxn is - 52.4 kcal/mol.

All living cells use ATP for capture, transfer, and storage of energy. The change
in free energy (G) to hydrolyze ATP (to ADP) is 12 kcal/mol. The energy to
make ATP comes from the energy released from fuel molecules such as glucose.
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The Logic of Glycolysis

Importance of Phosphorylated
Intermediates:
The phosphorylated intermediates
(each carrying a net negative charge)
cannot diffuse out of the cell, since the
plasma membrane is impermeable to
charged molecules.
Phosphate groups are essential
components in the enzymatic
conservation of metabolic energy.
Binding of phosphate groups to the
active sites of enzymes provides
binding energy, lowering the activation
energy and increasing the specificity of
enzymatic reactions.

Energy Available in Oxidation of Nutrients is

Released in Small Steps in Cellular Metabolism

Key Intermediates of Glucose Metabolism

The mitochondrial inner

membrane and matrix are
the sites of most reactions
involving the oxidation of
pyruvate and the coupled
synthesis of ATP

Energetically
unfavorable
reactions in
cells are often
coupled to the
hydrolysis of
ATP.

An analogy for cellular respiration

The metabolism of glucose is
highly exergonic (G for
complete conversion of
glucose is 686 kcal/mol) .

G < 0

G < 0
G < 0

This process has many steps

and is carefully controlled.
The available free energy
drives the endergonic
formation of NADH and ATP.

A multistep open hydroelectric system.

Cellular respiration is analogous to this system: Glucose is broken
down in a series of exergonic reactions that power the work of the cell.
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The Structure and Hydrolysis of ATP

ATP (adenosine triphosphate)

Is the cells energy shuttle

Provides energy for cellular functions
Adenine
N
O

-O
O-

O-

CH2

C
N
CH

C
N

OH

Phosphate groups

HC

NH2

H
OH

Ribose

OH
21

 Energy is released from ATP

When the terminal phosphate bond is broken

Adenosine triphosphate (ATP)

H2O

Figure 8.9 Inorganic phosphate

Adenosine diphosphate (ADP)

Energy

22

 Energy coupling
ATP powers cellular work by coupling exergonic reactions to
endergonic reactions

Catabolic pathways drive the regeneration of ATP from ADP and

phosphate
ATP drives endergonic reactions by phosphorylation, transferring a
phosphate to other molecules

A cell does three main kinds of work

Mechanical
Transport

Chemical
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 The three types of cellular work

Are powered by the hydrolysis of ATP
P

Motor protein

Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein

ADP

ATP

P
P

Solute

Solute transported

(b) Transport work: ATP phosphorylates transport proteins

Glu +

NH2

NH3

Reactants: Glutamic acid

and ammonia

Glu
Product (glutamine)
made

(c) Chemical work: ATP phosphorylates key reactants

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ATP is the Energy Currency of the Cell

The useful free energy in an ATP molecule is
contained in phosphoanhydride bonds.
Exergonic reactions are coupled to the
endergonic reaction of making ATP.

Enzymes Catalyze Metabolic Reactions

Most biological catalysts are proteins called enzymes. Some enzymes have
important contributing molecules that participate in the catalysis, such as some
types of vitamins and metal ions.
Enzymes bind specific reactant molecules called substrates. Substrates bind to
a particular site on the enzyme surface called the active site, where catalysis
takes place.
Binding a substrate to the active site produces an enzymesubstrate complex.
Hydrogen bonding, ionic attraction, or covalent bonding acting individually or
together hold these complexes together.
In general, enzyme activity must be regulated. This regulation contributes to
cell homeostasis, the maintenance of a stable internal state best suited to cell
survival.
Allosteric effects regulate metabolism. One way to control the whole pathway
is to have the end-product inhibit the first step in the pathway.

Enzymes accelerate biochemical reactions

by reducing transition-state free energy

Enzyme Mechanisms
Enzymes orient substrates.
While free in solution, substrates tumble and collide. The probability for the
collision at the angle necessary to change chemical interactions is low. When
bound to enzymes, two substrates can be oriented such that a reaction is more
likely.
Enzymes add charges to substrates.
The R groups (side chains) of an enzymes amino acids may directly participate in
making substrates more chemically reactive.
Some enzymes work by what is called acid-base catalysis. Acidic or basic side
chains of amino acids form the active site and transfer H+ to or from the
substrate, destabilizing a covalent bond in a substrate.
Some have metal ion cofactors, which involve the gain or loss of electrons, called
oxygen-reduction (redox) reactions.
Some enzymes induce strain in the substrate.
The stretching of the bonds decreases their stability, making them more reactive to
water.

Enzyme-Substrate Complexes are Highly Specific

Lock and Key Model

Induced Fit Model

 The catalytic cycle of an enzyme

1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).

Substrates

Enzyme-substrate
complex

6 Active site
Is available for
two new substrate
Mole.
Enzyme

5 Products are
Released.

Figure 8.17

Products

2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.

3 Active site (and R groups of

its amino acids) can lower EA
and speed up a reaction by
acting as a template for
substrate orientation,
stressing the substrates
and stabilizing the
transition state,
providing a favorable
microenvironment,
participating directly in the
catalytic reaction.

4 Substrates are
Converted into
Products.

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Factors affecting Enzyme Activity

To operate, some enzymes require added molecules
Cofactors are inorganic ions such as copper, zinc, and iron that bind temporarily to
certain enzymes and are essential to their function
Coenzymes are carbon-containing molecules required for the action of one or more
enzymes. Some coenzymes are vitamins. ATP and ADP are coenzymes.
Coenzymes must react with an enzyme, separate, and then participate in other
reactions.
Prosthetic groups are permanently bound to enzymes. They include the heme
groups (iron-containing organic molecules) that are attached to hemoglobin.
Enzymes and their environment
Some enzymes are tolerant to a wide range of pH and temperatures, while other
enzymes are very sensitive.
pH can influence the charges of carboxyl groups in neutral or basic solutions and
amino groups in neutral or acidic solutions.
In general, an increase in temperature (to a point) increases the rate of an enzymecatalyzed reaction. Temperature can negatively influence shape by breaking
hydrogen bonds. All enzymes show an optimal temperature for activity.

Effects of Temperature and pH

Each enzyme
Has an optimal temperature in which it can
function
Optimal temperature for
typical human enzyme

Optimal temperature for

enzyme of thermophilic

Rate of reaction

(heat-tolerant)
bacteria

20

40
Temperature (C)
(a) Optimal temperature for two enzymes

80

100

Figure 8.18
32

 Has an optimal pH in which it can function

Optimal pH for pepsin

(stomach enzyme)
Rate of reaction

Optimal pH
for trypsin
(intestinal
enzyme)

3
4
0
2
1
(b) Optimal pH for two enzymes

Figure 8.18

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Allosteric enzymes
Allosteric enzymes may have interacting subunits that change in shape and
function and modulate their catalytic activity. Allosteric enzymes are controlled
by effector molecules, that bind to an allosteric site, which is separate from the
active site. This binding changes the structure and function of the enzyme.
Depending on the particular enzyme, the binding may enhance or diminish
reactions at the active site.
Some allosteric enzymes have multiple active sites. When one binding site is
occupied, it changes the other(s) so they bind additional substrate molecules
more readily. This changes the shape of the reaction rate versus concentration
curve compared to non-allosteric enzymes. The advantage to the system is that
the enzyme's catalytic rate becomes concentration sensitive and responsive.
Allosteric enzymes usually have more than one type of subunit. A catalytic
subunit has an active site that binds the enzyme's substrate. A regulatory subunit
has one or more allosteric sites that bind specific effector molecules. In the
active state, the active sites on the catalytic subunits can bind substrate. In the
inactive state, the allosteric sites on the regulatory subunits can accept inhibitor.

 Feedback inhibition Enzyme regulation

Active site
available

In feedback
inhibition
The end
product of a
metabolic
pathway
shuts down
the pathway

Initial substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)

Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition

Active site of
enzyme 1 no
longer binds
threonine;
pathway is
switched off

Enzyme 2
Intermediate B

Enzyme 3

Intermediate C
Isoleucine
binds to
allosteric
site

Enzyme 4
Intermediate D
Enzyme 5

End product
(isoleucine)

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