Alberts • Johnson • Lewis • Morgan • Raff • Roberts • Walter

Molecular Biology
of the Cell
Sixth Edition

Chapter 2
Cell Chemistry and Bioenergetics

Copyright © Garland Science 2015

 CHAPTER CONTENTS

• THE CHEMICAL COMPONENTS OF A CELL

• CATALYSIS AND THE USE OF ENERGY BY CELLS

• HOW CELLS OBTAIN ENERGY FROM FOOD

The main elements in cells highlighted in the periodic table.

Red-99% of the total number of atoms present in the human body.

blue- 0.9% of the total.
green- trace amounts
yellow-unclear
 THE CHEMICAL
COMPONENTS OF A CELL
• C, H, N and O make up 96.5% of an organism’s
weight.

• The atoms of these molecules are linked together

by covalent bonds to form molecules.

• Cells are 70% water and life largely depends on

chemical reactions that take place in aqueous
solution.
Introduction
Introduction
Introduction
Introduction
Introduction
Introduction
Introduction
Introduction
Some energies important for cells.
 THE CHEMICAL
COMPONENTS OF A CELL
• Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
Water Is Held Together by Hydrogen Bonds
 THE CHEMICAL
COMPONENTS OF A CELL
• Four Types of Noncovalent Attractions Help Bring
Molecules Together in Cells
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Schematic indicating how two macromolecules with complementary surfaces
can bind tightly to one another through noncovalent interactions
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
Ball and stick model of a typical hydrogen bond
The most common hydrogen bonds in cells
 THE CHEMICAL
COMPONENTS OF A CELL
• Some Polar Molecules Form Acids and Bases in
Water
Protons readily move in aqueous solutions
 THE CHEMICAL
COMPONENTS OF A CELL
• A Cell Is Formed from Carbon Compounds
 THE CHEMICAL
COMPONENTS OF A CELL
• Cells Contain Four Major Families of Small Organic
Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
Cells Contain Four Major Families of Small Organic Molecules
 THE CHEMICAL
COMPONENTS OF A CELL
• The Chemistry of Cells Is Dominated by
Macromolecules with Remarkable Properties
The distribution of molecules in cells
Three families of macromolecules
Condensation and hydrolysis as opposite reactions

Each polymer grows by the addition of Molecules are broken down by

monomer onto the end of a growing hydrolysis.
chain in a condensation reaction, in
which one water molecule is lost with The condensation reactions are
each subunit added. energetically unfavorable; thus
polymer formation requires an
energy input.
 THE CHEMICAL
COMPONENTS OF A CELL
• Noncovalent Bonds Specify Both the Precise Shape
of a Macromolecule and Its Binding to Other
Molecules
The folding of proteins and RNA molecules into a particularly stable
3-D shape, or conformation

• Most of the covalent bonds in a

macromolecule allow rotation of the atoms
they join, giving the polymer chain great
flexibility.

• In principle, this allows a macromolecule to

adopt an almost unlimited number of
shapes, or conformations as random
thermal energy causes the polymer chain to
writhe and rotate.

• However, the shapes of most biological

macromolecules are highly constrained
because of the many weak noncovalent
bonds that form between different parts of
the same molecule.
Small molecules become covalently linked to form macromolecules,
which in turn assemble through noncovalent interaction
 CATALYSIS AND THE USE
OF ENERGY BY CELLS
• Living things create and maintain order, in a
universe that is tending always to greater disorder.

• To create this order, the cells in a living organism

must perform a never ending stream of chemical
reactions.

• Each cell can be viewed as a tiny chemical factory,

performing many milllions of reactions every
second.
Biological structures are highly ordered

(a) Protein molecules in the coat of a virus

(b) The regular array of microtubules seen in cross section of a
sperm tail
(c) Surface contours of a pollen grain
(d) Cross section of a fern stem
(e) A spiral arrangement of leaves in a succulent plant
 Cell Metabolism Is Organized by Enzymes

• The chemical reactions that a cell carries out

would normally occur only at much higher
temperatures than those existing inside cells.

• Enzymes are the catalysts that eases the

chemical reactions otherwise would not happen in
the cellular chemical environment.
• Mostly proteins, but there are also RNA catalysts
called ribozymes.

• The product of one reaction could be the substrate

of the other.
How a set of enzyme-catalyzed reactions generates a metabolic pathway

• Enzyme-catalyzed reactions are connected in series, so that the

product of one reaction becomes the starting material, or substrate,
for the next.

• Each enzyme catalyzes a particular reaction

• Enzymes remain unchanged
• Two opposing streams of chemical reactions occur
in cells:
(1)The catabolic patways breakdown foodstuffs
into smaller molecules, thereby generating both
energy and some of the small molecules that the
cell needs as building blocks

(2)The anabolic or biosynthetic pathways use

the small molecules and the energy harnessed by
catabolism to drive the synthesis of the many
other molecules that form the cell.

Anabolic pathways versus catabolic pathways – They

constitute metabolism
Schematic representation of the relationship between catabolic and
anabolic pathways in metabolism
 CATALYSIS AND THE USE
OF ENERGY BY CELLS
• Biological Order Is Made Possible by the Release of
Heat Energy from Cells
• The second law of thermodynamics – tendency of
things to become disordered
• Entropy – the measure of disorder
• First law of thermodynamics – energy cannot be
created or destroyed but it can be converted to
other forms
Biological Order Is Made Possible by the Release of Heat Energy
from Cells
A simple thermodynamic analysis of a living cell
Some interconversions between different forms of energy
Cells Obtain Energy by the Oxidation
of Organic Molecules
• All animal and plant cells are powered by energy
stored in the chemical bonds of organic molecules,
whether they are sugars that a plant has
photosynthesized as food for itself or the mixture
of large and small molecules that an animal has
eaten.

• Organisms must extract this energy in usable form

to live, grow and reproduce.

• Energy is extracted from food molecules by a

process of gradual oxidation, or controlled
burning.
Photosynthesis and respiration as complementary processes in the living
world.

• Photosynthesis converts the electromagnetic energy in sunlight

into chemical bond energy in sugars and other organic molecules.

• The organic molecules produced by photosynthesis in turn serve

as food for other organisms. Many of these organisms carry out
aerobic respiration, a process that uses O2 to form CO2.
The carbon cycle. Carbon atoms are incorporated into organic molecuels by
the photosynthetic activity of plants, algae and bacteria. They pass to
animals, microorganisms and organic matter in soil and oceans in cyclic
paths. CO2 is restored to the atmosphere when organic molecules are
oxidized by cells or burned by humans as fuels.
 Oxidation and Reduction Involve
Electron Transfers
• Oxidation/reduction reactions- any reaction in which
electrons are transferred from one atom to another.
• Oxidation –removal of the electrons
• Reduction- addition of electrons

• When a molecule in a cell picks up an electron, it often

picks up a proton at the same time (protons being freely
available in water). The net effect in this case is to add a
hydrogen atom to the molecule.
• A + e- + H + AH

• Hydrogenation reactions are reductions.

• Dehydrogenation reactions are oxidations.
Oxidation and Reduction Involve Electron Transfers

•Reduction: The number of C-H bonds

increases.

•Oxidation: The number of C-H bonds

decreases.
 Enzymes Lower the Activation-Energy
Barriers That Block Chemical Reactions
• Chemical reactions proceed spontaneously only in
the direction that leads to a loss of free energy.

• However the book in your hands does not burst

into flames. Because the molecules both in the
living organism and in the book are in a relatively
stable state and they cannot be changed to a
state of lower energy without an input of energy: a
molecule requires activation energy- a kick over
an energy barrier- before it can undergo a
chemical reaction that leaves it in a more stable
state.
 Enzymes Lower the Activation-Energy
Barriers That Block Chemical Reactions
• The chemistry in a living cell is tightly controlled,
the kick over energy barriers is greatly aided by a
specialized class of proteins- the enzymes.

• Each enzyme binds tightly to one or more

molecules called substrates.

• A substance that can lower the activation energy

of a reaction is termed a catalyst.

• Enzymes are among the most effective catalysts

known: some are capable of speeding up reactions
by factors of 1014 or more.
Enzymes Lower the Activation-Energy Barriers That Block Chemical
Reactions
Lowering the activation energy greatly increases the probability of a
reaction.
 Enzymes Can Drive Substrate Molecules
Along Specific Reaction Pathways
• Enzymes are both highly selective and very
precise, usually catalizing only one particular
reaction.
• The success of living organisms is attributable to a
cell’s ability to make enzymes of many types, each
with precisely specified properties.

• Each enzyme has a unique shape containing an

active site, a pocket or groove in the enzyme in to
which particular substrates will fit. Selective
substrate recognition

• Enzymes remain unchanged after reaction and can

function over and over again.
Directiing substrate molecules through a specific reaction pathway
by enzyme catalysts.
Enzymes Can Drive Substrate Molecules Along Specific Reaction
Pathways
 The Free-Energy Change for a Reaction, G,
Determines Whether It Can Occur
Spontaneously
• Enzymes directly couple energetically favorable
reactions, which release energy and produce heat, to
energetically unfavorable reactions, which produce
biological order.
• Free Energy is an expression of the energy available
to do work, i.e. the work of driving chemical reactions
• Energetically favorable reactions are those that
decrease free energy; thus have a negative G.

• Examples: Release of spring – Salt dissolution in water –

Energetically favorable
• Joining of amino acids to form peptide bond–
Energetically unfavorable

• These reactions can take place only if they are coupled

to a second reaction with a negative G so large that
the G of overall process is negative.
The distinction between energetically favorable and unfavorable
reactions
How reaction coupling is used to drive energetically unfavorable
reactions
A mechanical model illustrating the pirinciple of coupled chemical
reactions
 The Free-Energy Changes of Coupled
Reactions Are Additive
• Overall free energy change for a set of coupled
reactions is the sum of the free energy changes in each
of its component steps. Consider two sequential
reactions: X Y and Y Z whose G values are +5 and
-13 kJ/mole, respectively.

• If these two reactions occur sequentially, the G for the

coupled reaction will be -8 kJ/mole. This means that with
the appropriate conditions, the unfavorable reaction X
Y can be driven by the favorable reaction Y Z,
provided that this second reaction follows the first.

• Several of the reactions that convert sugars into CO2

and H2O have positive G values. But the pathway
nevertheless proceeds because the total G for the
series of sequential reactions has a large G value.
 Activated carrier molecules are essential
for biosynthesis
• Forming a sequential pathway is not adequate for
many purposes. Fortunately there are other more
general ways of using enzymes to couple reactions
together. These often involve the activated carrier
molecules.

• The energy released by the oxidation of food

molecules must be stored temporarily before it can
be channeled into the construction of many other
molecules needed by the cell. In most cases the
energy is stored as chemical-bond energy in a
small set of activated carrier molecules, which
contain one or more energy ricj covalent bonds.
 Activated carrier molecules are essential
for biosynthesis
• Activated carrier molecules diffuse rapidly hrouhout
the cell and thereby carry their bond energy from
sties of energy production to the sites where
energy will be used for biosynthesis and other cell
activities.

• The activated carriers store energy in an easily

exchangeable form, either as a readily transferable
chemical group or as electrons held at a high
energy level.

• The most important of the activated carrier

molecules are ATP and two molecules that are
closely related to each other NADH and NADPH.
Activated Carrier Molecules Are Essential for Biosynthesis
 ATP Is the Most Widely Used Activated
Carrier Molecule
• ATP is synthesized in an energetically unfavorable
phosphorylation reaction in which a phosphate
group is added to ADP.
• When required, ATP gives up its energy packet
through its energetically favorable hydrolysis to ADP
and inorganic phosphate
• ATP hydrolysis is coupled to many otherwise
unfavorable reactions. Many of these coupled
reactions involve the transfer of a terminal
phosphate in ATP to other molecule.
• ATP is the principle energy currency. Examples:
• Supplies energy for the pumps that perform matter
transport across the cellular membranes
• Powers the molecular motors that enables muscles
to contract
The hydrolysis of ATP to ADP and inorganic phosphate.
An example of a phosphate transfer reaction
Energy Stored in ATP Is Often Harnessed to Join Two Molecules
Together
 NADH and NADPH Are Important Electron
Carriers
• NAD+ (nicotinamide adenine dinucleotide) and
NADP+ (nicotinamide adenine dinucleotide
phosphate)
• Carries packet of energy corresponding to two
electrons plus a proton (H+).
• Substrates are oxidized and an Hydride ion (H-) is
added to these molecules forming NADH and
NADPH.

• NADPH in anabolic reactions, whereas NADH as an

intermediate in catabolic reactions
• [NAD+]/[NADH] high – oxidizing agent in
catabolism
• [NADP+ ]/[NADPH] low –reducing agent in
anabolism
NADH and NADPH Are Important Electron Carriers
NADH and NADPH Are Important Electron Carriers
 There Are Many Other Activated Carrier
Molecules in Cells
• Coenzyme A carries a readily transferable acetyl
group in a thioester linkage and in this activated
form is known as acetyl coenzyme A.

• FADH2 (flavin adenine dinucleotide) is a carrier of

hydrogens and high energy electrons
The structure of acetyl CoA
FADH2 is a carrier of hydrogens and high energy electrons
There Are Many Other Activated Carrier Molecules in Cells
 The Synthesis of Biological Polymers Is
Driven by ATP Hydrolysis
• Macromolecules are made from subunits that are
linked together in a condensation reaction in which
the constituents of a water molecule are removed
from two reactants.

• Consequently the reverse reactşon the breakdown

of all three types of polymers occurs by enzyme
catalyzed addition of water.

• The nucleic acids, proteins and polysaccharides

are all polymers that are produced by the repeated
addition of a monomer onto one end of a growing
chain.
The Synthesis of Biological Polymers Is Driven by ATP Hydrolysis
An alternative pathway of ATP hydrolysis in which pyrophosphate is first
formed then hydrolyzed
The head growth of polymers is compared with its alternative tail growth
 HOW CELLS OBTAIN ENERGY
FROM FOOD
• From the chemical bond energy in food molecules

• The proteins, lipids and polysachharides that make

up most of the food we eat must be broken down
into smaller molecules before our cells can use
them, either as a source of energy or as building
blocks for other molecules.

• Enzymatic digestion breaks down the large

polymeric molecules in food into their monomer
subunits.

• After digestion small organic molecules derived

from food enter the cytosol of cells where their
gradual oxidation begins.
Schematic representation of the controlled stepwise oxidation of sugar in a
cell, compared with ordinary burning.
 Glycolysis Is a Central ATP-Producing
Pathway
• The major process for oxidizing sugars is the
sequence of reactions known as glycolysis.

• Glycolysis produces ATP without the involvement

of molecular oxgen (O2).

• It occurs in the cytoplasm of most cells.

• Glycolysis probably evolved early in history of life,

before photosynthetic organisms introduced
oxygen into the atmosphere.
Glycolysis Is a Central ATP-Producing Pathway

• Each of the 10 steps shown is

catalyzed by a different enzyme.

• Step 4 cleaves a six-carbon sugar

into two three-carbon sugars, so
that the number of molecules at
every stage after this doubles.

• Results in net synhtesis of 2 ATP

and 2 NADH molecules per
molecule of glucose.
Glycolysis Is a Central ATP-Producing Pathway
Fermentations Produce ATP in the Absence
of Oxygen
• For many anaerobic organisms, which do not
utilize molecular oxygen, glycolysis is the principal
source of the cell’s ATP.

• Certain animal tissues, such as skeletal muscle,

can also continue to function using glycolysis
when molecular oxygen is limited.

• Yeast- alchololic fermentation

• Muscle-lactate fermentation
Two pathways for the anaerobic breakdown of pyruvate
Glycolysis Illustrates How Enzymes Couple
Oxidation to Energy Storage
• https://www.youtube.com/watch?v=8qij1m7XUhk

https://www.youtube.com/watch?v=8qij1m7XUhk
Schematic view of the coupled reactions that form NADH and ATP in
steps 6 and 7 of glycolysis
Organisms Store Food Molecules in Special
Reservoirs
• All organisms need to maintain a high ATP/ADP ratio to
keep biological order.

• Animals only have periodic acess to food and plants

survive overnight without sunlight.

• To compensate for long periods of fasting, animals store

fatty acids as fat droplets composed of water-insoluble
triacylglycerols. The triacylglycerols in animals are
mostly stored in the cytoplasm of specialized fat cells
called adipocytes.

• For shorter-term storage, sugar is stored as glucose

subunits in the larger branched polysaccharide
glycogen, which is present in the cytoplasm of many
cells, including liver and muscle.
The storage of sugars and fats in animal and plant cells
Organisms Store Food Molecules in Special
Reservoirs
• An average adult human stores enough glycogen for
only about a day of normal activities, but enough fat to
last for nearly a month.

• The sugar and ATP needed by plant cells are largely

produced in seperate organalles: sugars in chloroplasts
and ATP in mitochondria.

• During periods of excess photosynthetic activity during

the day, chloroplasts convert some of the sugars that
they make into fats and into starch, a polymer of
glucose, analogous to the glycogen of animals.

• The fats in plants are triacylglycerols just like the fat in

animals and differ only in the types of fatty acids that
predominate.
How sugars are produced from glycogen
Most Animal Cells Derive Their Energy from
Fatty Acids Between Meals
• After a meal, most of the energy that an animal
needs is derived from sugars obtained from food.
Excess sugars, are used to replenish depleted
glycogen stores or to synthesize fats as a food
store.

• Low glucose levels in the blood trigger breakdown

of fats for energy production.

• Animals convert sugars to fats but cannot convert

fatty acids to sugars. Instead the fatty acids are
oxidized directly.
How stored fats are mobilized for energy production in animals
 Sugars and Fats Are Both Degraded to
Acetyl CoA in Mitochondria
• In aerobic metabolism, the pyruvate that was
produced by glycolysis from sugars in the cytosol
is transported into the mitochondria of eukaryotic
cells. There it rapidly decarboxylated by a complex
of three enzymes, called the pyruvate
dehydrogenase complex. The products are a
molecule of CO2, NADH and acetyl CoA.

• The fatty acids imported from bloodstream are

moved into the mitochondria and oxidized.
Pathways for the production of acetyl coA from sugars and fats
The oxidation of fatty acids to acetyl coA
 The Citric Acid Cycle Generates NADH by
Oxidizing Acetyl Groups to CO2
• In the nineteenth century biologists noticed that in
the absence of air, cells produced lactic acid or
ethanol while in its rpesence they consume O2
and produce CO2 and H2O.
• In 1937, citric acid cycle, or Krebs cycle, was
discovered.
• The citric cycle takes place inside the
mitochondria and major ends products are CO2
and high energy electrons in the form of NADH.

• CO2 is released as a waste product, while the high

energy electrons from NADH are passed to a
membrane bound electron chain eventually
combining with O2 to produce H2O.
Simple overview of the citric acid cycle

•The reaction of acetyl CoA

with oxaloacetate starts the
cycle by producing citric acid.

•In each turn of the cycle, two

molecules of CO2 are produced
as waste products, plus 3
molecules of NADH, 1
molecule of GTP and 1
molecule of FADH2.
The structure of GTP
Glycolysis and the citric acid cycle provide the precursors needed to
synthesize many important biological molecules.

https://www.youtube.com/watch?v=ubzw64PQPqM&t=181s
Electron Transport Drives the Synthesis of
the Majority of the ATP in Most Cells
• Most chemical energy is released in the last stage
in the degradation of a food molecule. In this final
process, NADH and FADH2 transfer the electrons
that they gained to the electron trnasport chain,
which is embedded in the inner membrane of the
mitochondrion.

• As the electrons pass along this long chain of

specialized electron acceptor and donor
molecules, they fall to successively lower energy
states.

• The energy that the electrons release in this

process pumps H+ ions across the membrane
generating a gradient of H+ ions.
 Electron Transport Drives the Synthesis of
the Majority of the ATP in Most Cells
• The gradient serves as a major source of energy for cells,
being tapped like a battery to drive a variety of energy
requiring reactions.
• The most prominent of these reactions is the generation
of ATP by the phosphorylation of ADP.

• At the end of this series of electron transfers, the

electrons are passed to molecules of oxygen gas which
simultaneously combine with H+ from the surrounding
solution to produce water.

• The electrons have now reached a low enery level and

the food is completly oxidized. Oxidative phosphorylation

• In total, the complete oxidation of a molecule of glucose

to H2O and CO2 is used to make about 30 molecules of
ATP.
The final stages of oxidation of food molecules
 Amino Acids and Nucleotides Are Part of
the Nitrogen Cycle
• Although molecular nitrogen is abundant in the Earth’s
atmosphere, nitrogen is chemically unreactive as a gas.
Only a few living species are able to incorporate it into
organic molecules, a process called nitrogen fixation.

• Vertebrates receive all nitrogen from their dietary

intake of proteins and nucleic acids.

• About half of the 20 amino acids are essential for

vertebrates which means that they cannot be
synthesized from other ingredients of the diet.

• Humans and other animals cannot reduce sulfate

readily found on Earth, thus must acquire the sulfur
they need for their metabolism in the food that they
eat.
The nine essential amino acids
Metabolism Is Highly Organized and Regulated
 Metabolism Is Highly Organized and
Regulated
• All of these reactions occur in a cell that is less
than 0.1mm in diameter, and each requires a
different enzyme.

• Same molecule can often be a part of different

pathways

• Different cell types have specialized pathways.

• Nerve cells maintain almost no reserves of

glycogen or fatty acids and rely almost entirely on
a constant supply of glucose from the
bloodstream. In contrast, liver cells supply glucose
to actively contracting muscle cells.
https://www.youtube.com/watch?v=q-fKQuZ8dco