5

Ground Rules
of Metabolism
Links to Earlier Concepts
In this chapter, you will gain insight into the one-way flow
of energy through the world of life (Sections 1.1, 1.2) as you
learn more about specific types of energy (2.4) and the laws
of nature (1.8) that describe it. The chapter also revisits the
structure and function of atoms (2.2), molecules (2.3, 3.1–3.6),
and cells (4.3, 4.6, 4.7, 4.9).

Core Concepts
Organisms exchange matter and energy with the environment
in order to grow, maintain themselves, and reproduce.

Energy cannot be created or destroyed, but it can

be transferred and converted to other forms.
With each transfer or conversion, some energy
disperses. Maintaining the organization of living
systems requires ongoing inputs of energy to
offset this loss.

Organisms have various strategies to capture and store energy

for use in biological processes.

Cells store energy by building organic molecules,

and retrieve energy by breaking them down.
Many metabolic pathways couple energy-releasing
reactions with energy-requiring reactions. The
coupled reactions of electron transfer chains allow
cells to harvest energy from electrons in small,
manageable increments.

Cellular homeostasis requires maintenance of an internal

environment that differs from the external environment.

Homeostasis depends on constant movement

of substances across cell membranes, which are
not permeable to ions or most polar molecules.
Transport proteins and other membrane-crossing
mechanisms help cells maintain control over their
internal environment. Controls that govern steps
in metabolic pathways quickly shift cell activities in response to
changes in internal and external conditions.

A single-celled protist with the common name Sea Sparkle glows

blue when agitated—for example, by waves breaking on this
seashore in Maldives. The light is energy released from chemical 77
reactions that run inside these cells.

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 5.1 Life Runs on Energy
LEARNI NG OBJ ECTI VES
Describe entropy in terms of chemical bonding.
Compare kinetic energy with potential energy.
Use the first and second laws of thermodynamics to explain why the total
amount of energy available for doing work in the universe always decreases.

ENERGY DISPERSES
Energy is formally defined as the capacity to do work, but
this definition is not very satisfying. We do have an intuitive
understanding of energy just by thinking about familiar forms
of it, such as light, heat, electricity, and motion. We can also Figure 5.2 Feed conversion ratio. It takes more than 10,000
understand intuitively that one form of energy can be con- pounds of feed to raise a 1,000-pound steer. Where do the other
verted to another. Think about how a lightbulb changes elec- 9,000 pounds go? About half of the steer’s food is indigestible and
tricity into light, or how an automobile changes gasoline into passes right through it. The animal’s body breaks down molecules
in the remaining half to access energy stored in chemical bonds.
the energy of motion, which is called kinetic energy. Only about 15% of that energy goes toward building body mass.
The formal study of heat and other forms of energy is The rest is lost during energy conversions, as metabolic heat.
called thermodynamics (therm means heat; dynam means
power). By making careful measurements, thermodynamics
researchers discovered that the total amount of energy before the kitchen, and there is no longer a net (or overall) flow of
and after every conversion is always the same. In other words, heat from one area to another. Our system has now reached
energy cannot be created or destroyed—a phenomenon that its maximum entropy with respect to heat. The tendency of
is the first law of thermodynamics. entropy to increase is the second law of thermodynamics.
Energy also tends to spread out, or disperse, until no This is the formal way of saying that energy tends to spread
part of a system holds more than another part. In a kitchen, out spontaneously.
for example, heat always flows from a hot pan to cool air until Biologists use the concept of entropy as it applies to
the temperature of both is the same. We never see cool air chemical bonding, because energy flow in living things occurs
raising the temperature of a hot pan. Entropy is a measure of mainly by the making and breaking of chemical bonds. How
how much the energy of a particular system has become dis- is entropy related to chemical bonding? Think about it just
persed. We can use the hot pan in a cool kitchen as an exam- in terms of motion. Two unbound atoms can vibrate, spin,
ple of a system. As heat flows from the pan into the air, the and rotate in every direction, so they are at high entropy
entropy of the system increases (Figure 5.1). Entropy contin- with respect to motion. A covalent bond between the atoms
ues to increase until the heat is evenly distributed throughout restricts their movement, so they are able to move in fewer
ways than they did before bonding. Thus, the entropy of two
Figure 5.1 Entropy. Entropy tends to increase, which means
atoms decreases when a bond forms between them. Such
that energy tends to spread out spontaneously. The total amount entropy changes are part of the reason why some reactions
of energy in any system always stays the same. occur spontaneously and others require an energy input, as
you will see shortly.

heat
energy ENERGY’S ONE-WAY FLOW
Work occurs as a result of energy transfers. Consider how it
takes work to push a box across a floor. In this case, a body
Entropy

(you) transfers energy to another body (the box) to make it

move. The same principle applies in biological systems, for
example in a plant cell working to make sugars. Inside the cell,
one set of molecules harvests energy from light, then transfers
it to another set of molecules. The second set of molecules
Time uses the energy to build the sugars from carbon dioxide and

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 A Energy In
Sunlight reaches environments on Earth.
Producers in those environments capture
some of its energy and convert it to other
forms that can drive cellular work.

PRODUCERS

B Some of the energy

captured by producers
ends up in the tissues
of consumers.

CONSUMERS

C Energy Out
With each energy transfer, some energy
escapes into the environment, mainly as
heat. Living things do not use heat to drive
cellular work, so energy flows through the
world of life in one direction overall.

Figure 5.3 Energy movement through the world of life. Figure 5.4 Illustration of potential energy. By opposing the
Energy (yellow arrows) flows from the environment into living organ- downward pull of gravity, the rope attached to the rock prevents
isms, then back to the environment. The flow drives a cycling the man from falling. Similarly, a chemical bond that attaches two
of materials (green arrows) among producers and consumers. atoms keeps them from flying apart.

water. This particular energy transfer involves the conversion The energy that fuels most life on Earth comes from
of light energy to chemical energy. Most other types of cel- the sun. That energy flows through producers such as plants,
lular work occur by the transfer of chemical energy from one then consumers such as animals (Figure 5.3). During its jour-
molecule to another. ney, the energy is transferred many times. With each transfer,
Every time energy is transferred, a bit of it disperses— some energy escapes as heat until, eventually, all of it is per-
usually in the form of heat. As a simple example, a typical manently dispersed. However, the second law of thermody-
incandescent lightbulb converts only about 5 percent of the namics does not say how quickly the dispersal has to happen.
energy of electricity into light. The remaining 95 percent ends Energy’s spontaneous dispersal is resisted by chemical bonds.
up as heat that disperses from the bulb. The energy in chemical bonds is a type of potential energy,
Dispersed heat is not useful for doing work, and it is not which is energy stored in the position or arrangement of
easily converted to a more useful form of energy (such as elec- objects in a system (Figure 5.4). Think of all the bonds in
tricity). Because some of the energy in every transfer disperses the countless molecules that make up your skin, heart, liver,
as heat, and dispersed heat is not useful for doing work, we blood, and other body parts. Those bonds hold the molecules,
can say that the total amount of energy available for doing and you, together—at least for the time being.
work in the universe is always decreasing.
Is life an exception to this inevitable flow? An organized energy The capacity to do work.
body is hardly dispersed. Energy becomes concentrated in entropy (EN-truh-pee) Measure of how much the energy of a
system is dispersed.
each new organism as the molecules of life assemble and
first law of thermodynamics Energy cannot be created or
organize into cells. Even so, living things constantly use destroyed.
energy to grow, to move, to acquire nutrients, to reproduce, kinetic energy (kih-NEH-tick) The energy of motion.
and so on. Some energy is lost in every one of these processes potential energy Stored energy.
(Figure 5.2). Unless those losses are replenished with energy second law of thermodynamics Energy tends to disperse
from another source, life’s complex organization will end. spontaneously.

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 5.2 Energy in the Molecules of Life
LEARNI NG OBJ ECTI VES Reactants Products
Explain chemical bond energy. 2H2  O2 2H2O
Distinguish between endergonic and exergonic reactions. (hydrogen) (oxygen) (water)

Describe activation energy.

Explain how cells store and harvest energy using chemical reactions. 4 hydrogen + 2 oxygen 4 hydrogen atoms
atoms atoms + 2 oxygen atoms

Figure 5.5 Chemical bookkeeping.

In equations that represent chemical reactions, reactants are writ-
ten to the left of an arrow that points to the products. A number
All cells store and retrieve energy in chemical bonds of before a formula indicates the number of molecules. Atoms may
the molecules of life, and these activities occur by way of shuffle around in a reaction, but the same number of atoms that
reactions (Section 3.1). During a reaction, one or more enter the reaction remain at the reaction’s end.
reactants (molecules that enter a reaction and become
changed by it) become one or more products (molecules
that are produced by the reaction). Intermediate mol-
ecules may form between reactants and products. We
show a reaction as an equation in which an arrow points
from reactants to products:
6 6
glucose oxygen glucose oxygen
2H2  O2 2H2O C6H12O2 O2 C6H12O2 O2
(hydrogen) (oxygen) (water) Free Energy

A number before a chemical formula in such equations energy out

indicates the number of molecules; a subscript indicates
the number of atoms of that element per molecule. Note energy in
that atoms shuffle around in a reaction, but they never
disappear: The same number of atoms that enter a reac- 6 6 6 6
tion remain at the reaction’s end (Figure 5.5). carbon dioxide water carbon dioxide water
CO2 H2O CO2 H2O

CHEMICAL BOND ENERGY A Endergonic reactions B Exergonic reactions convert

convert molecules with lower molecules with higher free
Every chemical bond holds a certain amount of energy. free energy to molecules with energy to molecules with
That is the amount of energy required to break the bond, higher free energy, so they lower free energy, so they end
require a net energy input. with an energy release.
and it is also the amount of energy released when the
bond forms. The particular amount of energy held by Figure 5.6 The ins and outs of energy in chemical reactions.

?
a bond depends on which elements are taking part in
it. For example, two covalent bonds—one between an FIGURE IT OUT
oxygen and a hydrogen atom in a water molecule, the Which law of thermodynamics explains energy
inputs and outputs in chemical reactions?
other between two oxygen atoms in molecular oxygen Answer: The first law
(O2)—both hold energy, but different amounts of it.
Bond energy and entropy both contribute to a mol-
ecule’s free energy, which is the amount of energy that is
WHY EARTH DOES NOT
available (“free”) to do work. In most reactions, the free
energy of reactants differs from the free energy of prod-
GO UP IN FLAMES
ucts. If the reactants have less free energy than the prod- The molecules of life release energy when they combine with
ucts, the reaction will not proceed without a net energy oxygen. Think of how a spark ignites wood in a campfire.
input. Such reactions are endergonic, which means Wood is mostly cellulose, which consists of long chains of
“energy in” (Figure 5.6A). If the reactants have more free repeating glucose monomers (Section 3.2). A spark starts
energy than the products, the reaction will end with a net a reaction that converts cellulose (in the wood) and oxygen
release of energy. Such reactions are exergonic, which (in air) to water and carbon dioxide. The reaction is highly
means “energy out” (Figure 5.6B). exergonic, which means it releases a lot of energy—enough

80 U N I T 1 PRINCIPLES OF CELLULAR LIFE

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to initiate the same reaction with other cellulose and oxygen
molecules. That is why wood keeps burning after it has been
lit (Figure 5.7A).
Earth is rich in oxygen—and in potential exergonic reac-
tions with oxygen. Why doesn’t it burst into flames? Luckily,
chemical bonds do not break without at least a small input of
energy, even in an exergonic reaction. We call this input acti-
vation energy. Activation energy, the minimum amount of
energy required to get a chemical reaction started, is a bit like
a hill that reactants must climb before they can coast down
the other side to become products (Figure 5.7B).
Both endergonic and exergonic reactions have activation A Wood continues to burn after it has been lit. The reaction between
cellulose and oxygen releases enough energy to trigger the reaction
energy, but the amount varies with the reaction. Consider again with other molecules. Activation energy keeps this and other
guncotton (nitrocellulose), a highly explosive derivative of cel- exergonic reactions from starting without an energy input.
lulose. Christian Schönbein accidentally discovered a way to
manufacture it when he used his wife’s cotton apron to wipe Reactants:
up a nitric acid spill on his kitchen table, then hung it up to 2H2  O2
dry next to the oven. The apron exploded, and being a chemist
in the 1800s, Schönbein was thrilled. He immediately tried Activation energy
Free energy
marketing guncotton as a firearm explosive, but it was too
unstable to manufacture. So little activation energy is needed Difference between Products: 2H2O
to make guncotton react with oxygen that it tends to explode free energy of reactants
and free energy of products
unexpectedly. Several manufacturing plants burned to the
ground before guncotton was abandoned for use as a firearm
explosive. The substitute? Gunpowder, which has a higher Time
activation energy for a reaction with oxygen. B Most reactions will not begin without at least a small input of
energy. The minimum energy required to start a reaction started is
called activation energy, and it is shown on a graph as a bump in an
ENERGY IN, ENERGY OUT energy hill. This graph shows an energy-releasing reaction; energy-
requiring reactions also have activation energy.
Cells store energy by running endergonic reactions that build
Figure 5.7 Activation energy.
organic compounds (Figure 5.8A). For example, light energy
drives the overall reactions of photosynthesis, which produce
sugars such as glucose from carbon dioxide and water. Unlike energy in
light, glucose (and the energy in its bonds) can be stored in a
cell. Cells release stored energy by running exergonic reactions small organic
that break the bonds of organic compounds (Figure 5.8B). molecules compounds
endergonic reactions
(e.g., carbon (carbohydrates,
Most cells do this when they carry out the overall reactions of dioxide, water) fats, proteins)
aerobic respiration, which releases the energy of glucose by
breaking the bonds between its carbon atoms. You will see in A Cells run endergonic reactions to store energy in the bonds of
the next few sections how cells use energy released from some organic compounds.
reactions to drive others.
organic small
activation energy Minimum amount of energy required to start compounds molecules
exergonic reactions
a reaction. (carbohydrates, (e.g., carbon
endergonic (end-er-GON-ick) Describes a reaction that requires a fats, proteins) dioxide, water)
net input of free energy to proceed.
exergonic (ex-er-GON-ick) Describes a reaction that ends with a
net release of free energy. energy out
product A molecule that is produced by a reaction. B Cells run exergonic reactions to retrieve energy stored in the
reactant (ree-ACK-tunt) A molecule that enters a reaction and is bonds of organic compounds.
changed by participating in it. Figure 5.8 Cells store and retrieve energy in bonds.

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 5.3 How Enzymes Work
LEARNI NG OBJ ECTI VES enzyme substrates
Explain enzyme specificity. A An enzyme can act
Describe four ways that enzymes speed reactions. only on molecules that
“fit” its active site. Such
Using appropriate examples, explain how environmental factors affect molecules are called the
enzyme activity. enzyme’s substrates.

B An active site squeezes

substrates together, influ-
THE NEED FOR SPEED ences their charge, or
causes some change that
Metabolism requires enzymes. Why? Consider the break-
lowers activation energy,
down of sugar to carbon dioxide and water. That reaction so the reaction proceeds.
can occur on its own, but it might take decades. The same
conversion takes just seconds inside your cells. Enzymes make C The product leaves
the difference. In a process called catalysis, an enzyme makes the active site after the
reaction is finished. The
a reaction run much faster than it would on its own (in other
enzyme is unchanged, so
words, it catalyzes the reaction). The enzyme is unchanged by it can work repeatedly.
participating in the reaction, so it can work again and again.
Some enzymes are RNAs, but most are proteins. Each
has one or more active sites, which are pockets where cataly-
sis occurs (Figure 5.9). An enzyme acts only on molecules
that “fit” its active site—those complementary in shape, size,
polarity, and charge. Such molecules are called the enzyme’s
substrates. Some enzymes have multiple substrates, but each
catalyzes a specific reaction or set of reactions.
When we talk about activation energy, we are really
talking about the energy required to bring reactant bonds to
D Left, a glucose molecule meets up with a phosphate in the active
their breaking point. Before a reaction, there are molecules of site of hexokinase. Right, the enzyme has catalyzed the reaction,
reactants. After the reaction, there are molecules of products. and the product, glucose-6-phosphate, is leaving its active site.
What happens in between? At a particular moment between Notice how the active site changes shape.
reactants and products, existing bonds begin to break and
Figure 5.9 The active site. Each enzyme acts only on molecules
new bonds begin to form. At that in-between state, which is
(substrates) that “fit” its active site. For simplicity, active sites are
called the transition state, the reaction can run without any often depicted as blobs or geometric shapes (A –C ). The models in D
additional energy input. show the actual contours of an active site in hexokinase, an enzyme
Enzymes help bring reactants to the transition state by that adds a phosphate group to glucose and other six-carbon sugars.
lowering activation energy (Figure 5.10). They do so by the
following four mechanisms.
1. Entering an active site brings substrates in close physi- Transition state
cal proximity. The closer the substrates are to one another, the
Activation energy
more likely they are to react.
without enzyme Activation energy
2. Substrate molecules in a solution collide from random
Free energy

with enzyme
directions. By contrast, an active site orients substrates in Reactants
positions that favor reaction.
Products
3. By the induced-fit model, the “perfect” fit between
active site and substrate occurs at the transition state. A
substrate molecule that enters the active site is not exactly Time
complementary to it; interacting with the substrate causes Figure 5.10 The transition state. An enzyme enhances the
the active site to change shape so that the fit between them rate of a reaction by lowering activation energy.

?
improves. This shape change is necessary for catalysis to occur.
4. Metabolism occurs in water-based fluids, but water FIGURE IT OUT
molecules can interfere with certain reactions. Active sites of Is the reaction shown in the graph endergonic or
exergonic?
Answer: Exergonic
some enzymes repel water, keeping it away from the reaction.

82 U N I T 1 PRINCIPLES OF CELLULAR LIFE (9D) Image of PDB ID: 1HKC, Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB,
C R E D I T:
The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain
hexokinase complexed with glucose and glucose-6-phosphate Structure 1998 Jan 15;6(1):39–50; and Image of PDB
ID: 1HKB, Aleshin AE, Zeng C, Bartunik HD, Fromm HJ, Honzatko RB, Regulation of hexokinase I: crystal structure of
recombinant human brain hexokinase complexed with glucose and phosphate J Mol Biol. 1998 Sep 18;282(2):345–57
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created with PyMOL software fromin whole or in part. WCN 02-200-203
Schrödinger.
aa

Figure 5.11 An organism (and its enzymes) adapted to life

A S I A in a particular environment.
The Mariana Trench’s Challenger Deep, at almost 11,000 meters
(36,000 feet) below sea level, is Earth’s deepest spot. Here, despite
crushing pressure, shrimplike Hirondellea gigas swarm the ocean
floor. H. gigas grow up to 2 inches (5 centimeters) long, more than
twice the size of their common beachside relative, the sandhopper.
Very little organic carbon makes its way down into the Challenger
Deep, so how do H. gigas get enough food to grow so big? These
crustaceans were discovered to eat “wood fall,” which is tree and
plant debris swept into the ocean that occasionally sinks. If a ship
happened to sink into the Mariana Trench, “H. gigas would gladly
eat it,” said researcher Hideki Kobayashi. “In fact, a few of them bit
into the wooden parts of our camera system.” Special enzymes allow
H. gigas to digest the cellulose in wood. Not surprisingly, these wood-
busting enzymes work best under high-pressure conditions.

INFLUENCES ON ENZYME ACTIVITY

Environmental factors such as pH, temperature, and salt pepsin trypsin
A The pH-dependent
concentration influence an enzyme’s shape, which in turn activity of two digestive
influences its function (Section 3.4). Each enzyme works enzymes. Pepsin acts

Enzyme activity
best in a particular range of conditions that reflect the in the stomach, where
the normal pH is 2.
environment in which it evolved (Figure 5.11).
Trypsin acts in the small
Consider two enzymes that play a role in human intestine, where the pH
digestion (Figure 5.12A). The enzyme pepsin, which works is normally around 7.5.
best at low pH, begins the process of protein breakdown in 2 4 6 8 10
the very acidic environment of the stomach (pH 2). During pH
digestion, the stomach’s contents pass into the small intestine,
B The temperature-
where the pH rises to about 7.5. Pepsin denatures (unfolds) E. coli T. aquaticus
dependent activity of a polymerase polymerase
above pH 5.5, so this enzyme becomes inactivated in the small DNA synthesis enzyme
intestine. Protein breakdown continues with the assistance of from two species of
Enzyme activity

trypsin, an enzyme that functions well at the higher pH. bacteria: E. coli, which
inhabits the human
Adding heat boosts free energy, which is why the jiggling gut (normally 37°C);
motion of atoms and molecules increases with temperature. and Thermus aquati-
The greater the free energy of reactants, the closer they are cus, which lives in hot
to reaching activation energy. Thus, the rate of an enzymatic springs around 70°C.
20 40 60 80 100
reaction typically increases with temperature—but only up Temperature (°C)
to a point. An enzyme denatures above a characteristic tem- Figure 5.12 Enzymes, temperature, and pH.
perature (Section 3.5). Then, the reaction rate falls sharply Each enzyme functions best within a characteristic range of condi-
as the shape of the enzyme changes and it stops working tions—generally, the same conditions that occur in the environment
(Figure 5.12B). Body temperatures above 42°C (107.6°F) where the enzyme is normally found.
adversely affect the function of many of your enzymes, which
is why severe fevers are dangerous. active site Pocket in an enzyme where substrates react and are
The activity of enzymes is also influenced by the amount converted to products.

of salt in the surrounding fluid. Too little salt, and polar catalysis (cut-AL-ih-sis) The acceleration of a reaction rate by a
molecule that is unchanged by participating in the reaction.
parts of the enzyme attract one another so strongly that the
induced-fit model Substrate binding to an active site improves
enzyme’s shape changes. Too much salt interferes with the the fit between the two, thus inducing catalysis.
hydrogen bonds that hold the enzyme in its characteristic substrate Molecule that an enzyme acts upon and converts to a
shape, and the enzyme denatures. product; reactant in an enzyme-catalyzed reaction.

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 5.4 Metabolic Pathways
LEARNI NG OBJ ECTI VES reactant reactant
Describe metabolic pathways. enzyme 1 enzyme 1 enzyme 3
Use an example to explain how cells can control the activity of an enzyme.
intermediate
Describe how feedback inhibition affects a metabolic pathway.
enzyme 2
Explain the role of redox reactions in electron transfer chains. intermediate intermediate
intermediate
enzyme 3 product
Building, rearranging, or breaking down an organic molecule product enzyme 2
often occurs stepwise, in a series of enzymatic reactions called
a metabolic pathway. Many pathways are quite complex, A A linear pathway B The last step of a cyclic
involving thousands of molecules, and they interconnect in runs straight from pathway regenerates a reac-
reactant to product. tant for the first step.
an even more complex network that constitutes the cell’s
metabolism. Some pathways are linear, meaning that the reac- Figure 5.13 Metabolic pathways.
tions run straight from reactant to product (Figure 5.13A).
Others are cyclic. In a cyclic pathway, the last step regenerates active site substrate
a reactant of the first step (Figure 5.13B).
enzyme
CONTROLS OVER METABOLISM
A cell conserves energy and resources by making only what regulatory
it needs at any given moment—no more, no less. Several molecules
mechanisms help it maintain, raise, or lower the production Figure 5.14 Allosteric regulation, in which regulatory molecules
of thousands of different substances. Consider that reactions bind to a region of an enzyme that is not the active site. The binding
do not only run from reactants to products. Many also run changes the shape of the enzyme, and thus alters its activity.

?
in reverse at the same time, with some of the products being
FIGURE IT OUT
converted back to reactants: Is this enzyme’s activity enhanced or inhibited by
regulatory molecule binding?
Answer: Enhanced
reactant product

The rates of the forward and reverse reactions often depend

on the concentrations of reactants and products: A high
concentration of reactants pushes the reaction in the forward
direction, and a high concentration of products pushes it in
the reverse direction:
reactant X
enzyme 1
intermediate
enzyme 2
product

Figure 5.15 Feedback inhibition.

reactant product
Here, two different enzymes act in series to convert a reactant to a
reactant product product. The product inhibits the activity of the first enzyme.

Other mechanisms more actively regulate pathways.

The activity of many enzymes changes when regulatory mol-
ecules bind to them, for example. Some enzymes are active
only when they have an attached phosphate group; these
enzymes can be “switched on” by adding a phosphate group,
? FIGURE IT OUT
Is this metabolic pathway cyclic or linear?

in which a change that results from an activity decreases or

Answer: Linear

and “switched off ” by removing it. Regulatory molecule bind- stops the activity, is called feedback inhibition.
ing alters an enzyme’s shape in a way that enhances or inhibits A pathway that synthesizes the amino acid serine is reg-
its activity. The location of the binding site varies among ulated by feedback inhibition. The first enzyme in the path-
enzymes; if it occurs outside of the active site, the mechanism way has four binding sites for serine. When all four of these
of control is called allosteric regulation (Figure 5.14). sites are occupied by serine molecules, the enzyme becomes
Regulating a single enzyme can affect an entire metabolic inactive. When serine is being used faster than it is being
pathway. In some cases, the end product of a series of enzy- made, for example when protein synthesis is in high gear, its
matic reactions inhibits the activity of one of the enzymes in concentration in cytoplasm falls. Then, the enzyme releases
the series (Figure 5.15). This type of regulatory mechanism, the bound serines and becomes active again.

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 1 glucose
+ 2 1 An input of activation energy splits
+ e– glucose (C6H12O6) into hydrogen ions
oxygen H
carbon (H+), electrons (e¯), and carbon dioxide
dioxide (CO2).
+ 2 Electrons lose energy ( ) as they
water move through an electron transfer
3 chain. Energy released by the electrons
e– is harnessed for cellular work.
3 Electrons, hydrogen ions, and
oxygen combine to form water.

B In cells, glucose reacts with oxygen in a stepwise fashion that involves an electron transfer chain,
represented here by a staircase. Energy is released in amounts that cells are able to harness.

A Glucose reacts with oxygen (burns). Energy in the form of light and heat is released
all at once as carbon dioxide and water are produced.
Figure 5.16 Comparing uncontrolled and controlled energy release. The overall reaction is the same in both cases.

ELECTRON TRANSFERS next two chapters, you will learn about energy transfers in
Metabolic pathways that capture or release energy can be electron transfer chains. An electron transfer chain is a
dangerous for cells to run. The bonds of organic molecules series of membrane-bound enzymes and other molecules that
hold enough energy to be harmful if released all at once, for give up and accept electrons in turn. Electrons are at a higher
example by combustion (burning) reactions with oxygen energy level (Section 2.2) when they enter a chain than when
(Figure 5.16A). Most cells use oxygen to break the bonds they leave. Energy given off by an electron as it drops to a
of organic molecules, but they have no way to harvest the lower energy level is harvested by molecules of the electron
uncontrolled burst of energy released by burning. Instead, transfer chain to do cellular work (Figure 5.16B).
they break the bonds of an organic molecule one by one, in
steps that release energy in small, manageable amounts. These
Figure 5.17 Visible evidence of energy transferred during a
steps are reactions in metabolic pathways, and most are redox redox reaction: a glowing protist, Noctiluca scintillans. The path-
(oxidation–reduction) reactions. A typical redox reaction is way that produces the glow involves an enzyme called luciferase
an electron transfer, in which an electron is transferred from and its substrate, luciferin. It runs when the cells are mechanically
one molecule (which becomes oxidized when that happens) stimulated, as by waves (shown in the chapter opening photo) or an
attack by a protist-eating predator.
to another (which becomes reduced). To remember what
The pathway, summarized below, involves a redox reaction in which
reduced means, think of how the negative charge of an elec- luciferin is oxidized, and oxygen is reduced. Remember, energy is
tron “reduces” the charge of a recipient molecule. lost during every transfer. In this reaction, the electron loses energy
When an electron is transferred from one molecule to in the form of blue light during the transfer:
another, its energy is transferred too (Figure 5.17). In the luciferase
luciferin  2H+  O2 luciferin O  H2O  light

allosteric regulation (al-oh-STARE-ick) Control of enzyme activity

by a regulatory molecule that binds outside the enzyme’s active site.
electron transfer chain In a cell membrane, series of enzymes
and other molecules that accept and give up electrons, thus
releasing the energy of the electrons in steps.
feedback inhibition Regulatory mechanism in which a change
that results from some activity decreases or stops the activity.
metabolic pathway Series of enzyme-mediated reactions by
which cells build, remodel, or break down an organic molecule.
redox reaction (REE-docks) Oxidation–reduction reaction. In a
typical redox reaction, one molecule accepts electrons (it becomes
reduced) from another molecule (which becomes oxidized).

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 5.5 Cofactors
LEARNI NG OBJ ECTI VES
TABLE 5.1
Explain the difference between cofactors and coenzymes.
Give some examples of cofactors, and also of mechanisms by which Some Common Coenzymes
cofactors affect enzyme function. Coenzyme Example of Function
Describe phosphorylation and give an example. Ascorbic acid Collagen fiber formation; carries electrons
Explain why we say ATP is an important currency in a cell’s energy economy. (vitamin C) during peroxide breakdown (in lysosomes)
ATP Transfers energy with a phosphate group
NAD, NAD+ Carries electrons during glycolysis
NADP, NADPH Carries electrons, hydrogen atoms during
Most enzymes (and many other proteins) cannot function photosynthesis
properly without assistance from small molecules or metal FAD, FADH, FADH2 Carries electrons during aerobic respiration
ions. The assistants are called cofactors. Some essential CoA Carries acetyl group (COCH3) during
dietary vitamins and minerals are cofactors, and many others glycolysis
are converted into cofactors when they enter the body. Coenzyme Q10 Carries electrons in electron transfer chains
Metal ions can act as cofactors. These ions stabilize the of aerobic respiration
structure of many enzymes, in which case the enzyme dena- Biotin (vitamin B7) Carries CO2 during fatty acid synthesis
tures if the ions are removed. Metals also play a functional Heme Accepts and donates electrons
role in many reactions by interacting with electrons in nearby
atoms. Atoms of metal elements readily lose or gain electrons,
so a metal cofactor can help bring on the transition state by In some reactions, cofactors participate as separate
donating or accepting electrons, or simply by tugging on them. molecules. In others, they stay tightly bound to the enzyme.
Organic cofactors are coenzymes (Table 5.1 and Figure Catalase, an enzyme of peroxisomes, has four tightly bound
5.18). Coenzymes carry chemical groups, atoms, or electrons cofactors called hemes. A heme is a small organic compound
from one reaction to another, and often into or out of organ- with an iron atom at its center (Figure 5.19). Catalase’s
elles. Unlike enzymes, many coenzymes are modified by taking substrate, hydrogen peroxide (H2O2), is a highly reactive
part in a reaction. They are regenerated in separate reactions. molecule that forms during some normal metabolic reactions.
Consider NAD+ (nicotinamide adenine dinucleotide), a coen- Hydrogen peroxide is dangerous because it can easily oxidize
zyme derived from niacin (vitamin B3). NAD+ can accept and destroy the organic molecules of life, or form free radicals
electrons and hydrogen atoms, thereby becoming reduced to (Section 2.2) that do. Catalase neutralizes this threat. The
NADH. When electrons and hydrogen atoms are removed enzyme’s active site holds a hydrogen peroxide molecule close
from NADH (an oxidation reaction), NAD+ forms again: to a heme. Two H2O2 molecules alternately oxidize and then
reduce the heme’s iron atom, an interaction that causes the
NAD+  electrons  H+ NADH NAD+  electrons  H+ molecules to break down and form water.

Figure 5.18 Example of a coenzyme. Humans need but Figure 5.19 Heme. This organic molecule is part of the active
cannot make ascorbic acid, so we must get it in foods such as site in many enzymes (such as catalase). In other contexts, it carries
parsley and citrus fruits. The molecule, also called vitamin C, is a oxygen (e.g., in hemoglobin) or electrons (e.g., in molecules of
coenzyme in several important metabolic reactions, including one electron transfer chains). O
in a pathway that forms collagen fibers.
CH3 CH3
iron atom
Collagen is the main protein in extracellular matrix (ECM, Sec- HO
tion 4.10). In the absence of vitamin C, collagen fibers do not form
correctly and neither does ECM. Tissues such as skin become too CH2
fragile, so they bleed and become infected easily. These symptoms N N

are characteristic of scurvy, a disease that is fatal if untreated. Fe

N N
OH
CH3
OH HO
CH3
H2C

?
O
O ascorbic acid
O
(vitamin C) FIGURE IT OUT
Is heme a cofactor or a coenzyme?
Answer: It is both.
HO OH

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 Substances such as catalase that interfere with the oxida-
tion of other molecules are called antioxidants. Antioxidants adenine
minimize the amount of damage that cells sustain as a result
of oxidation by free radicals or other molecules, so they are three phosphate
essential to health. Oxidative damage is associated with many groups
diseases, including cancer, diabetes, and heart disease.
ribose

ATP—A SPECIAL COENZYME

A ATP. Bonds between its phosphate groups hold a lot of energy.
Many coenzymes are multifunctional molecules. In particular,
the nucleotide ATP (adenosine triphosphate, Section 3.6)
AMP ADP ATP
functions as a coenzyme in many reactions. Bonds between adenine
phosphate groups hold a lot of energy compared to other ribose P P P
bonds, and ATP has two of them holding its three phosphate
groups together (Figure 5.20A). When a phosphate group is B After ATP loses one phosphate group, the nucleotide is ADP
transferred to or from a nucleotide, this bond energy is trans- (adenosine diphosphate); after losing two, it is AMP (adenosine
ferred along with it. Thus, the nucleotide can receive energy monophosphate).

from an exergonic reaction, and it can donate energy to an ADP + Pi

energy out energy in
endergonic one. ATP in particular is such an
ATP important currency in a cell’s energy economy
that we use a cartoon coin to symbolize it.
A reaction in which a phosphate group is added to a ATP
molecule is a phosphorylation. ADP (adenosine diphos-
phate) forms when an enzyme transfers a phosphate group C The ATP/ADP cycle. ADP forms in a reaction that removes a
from ATP to another molecule during a phosphorylation phosphate group from ATP (Pi is an abbreviation for phosphate
group). Energy released in this exergonic reaction drives other
(Figure 5.20B). Cells constantly run this reaction in order
reactions that are the stuff of cellular work. ATP forms again in
to drive a variety of endergonic reactions. Thus, they must endergonic reactions that phosphorylate ADP.
constantly replenish their stockpile of ATP—by running
Figure 5.20 ATP, an important energy currency in metabolism.
exergonic reactions that phosphorylate ADP. The cycle of
using and then replenishing ATP is called the ATP/ADP cycle
(Figure 5.20C). organic compounds
(e.g., carbohydrates, fats, proteins)
The ATP/ADP cycle couples endergonic reactions with
exergonic ones (Figure 5.21). As you will see in Chapter 7, ADP + Pi
cells harvest energy from organic compounds by running
metabolic pathways that break them down. Energy released
in these pathways is captured in the high-energy phosphate
bonds of ATP molecules, and in electrons carried by coen- ATP
zymes. Both the ATP and the reduced cofactors that form
in these pathways can be used to drive many of the different
kinds of endergonic reactions that a cell runs. oxidized
coenzymes
antioxidant (ann-tee-OX-ih-dunt) Substance that interferes with
the oxidation of other molecules.
reduced
ATP/ADP cycle Process by which cells regenerate ATP. ADP forms coenzymes
when a phosphate group is removed from ATP, then ATP forms
again as ADP gains a phosphate group.
small molecules
coenzyme An organic cofactor. (e.g., carbon dioxide, water)
cofactor (KO-fack-ter) A molecule or metal ion that associates with
an enzyme and is necessary for its function. Figure 5.21 ATP and coenzymes couple endergonic reactions
phosphorylation (foss-for-ih-LAY-shun) Reaction in which a with exergonic reactions. Yellow arrows indicate energy flow.
phosphate group is added to a molecule. Compare Figures 5.8 and 5.20C.

C H A P T E R 5 GROUND RULES OF METABOLISM 87

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 5.6 Diffusion and Membranes
LEARNI NG OBJ ECTI VES hydrophobic molecules large uncharged polar
Name five factors that influence the rate and direction of diffusion. (steroids, fats, oils) molecules (glucose)
gases (O2, CO2, N2) ions (Na+, H+, HCO3–)
Describe tonicity and how it determines the direction of osmosis.
small uncharged charged molecules
Explain the relationship between turgor and osmotic pressure. polar molecules (proteins, nucleic
(H2O, ethanol, urea) acids, amino acids)

FACTORS THAT AFFECT DIFFUSION

Reactants and products of metabolic pathways constantly
move into, through, and out of cells. Diffusion, the spontane-
ous spreading of atoms or molecules through a fluid or gas, is
Figure 5.22 Selective permeability of lipid bilayers.
an essential way in which this movement occurs. An atom or Hydrophobic molecules, gases, and small uncharged polar
molecule is always jiggling, and this internal movement causes molecules can cross a lipid bilayer on their own. Ions, charged
it to randomly bounce off of nearby objects, including other molecules, and large uncharged polar molecules cannot.
atoms or molecules. Rebounds from such
collisions propel solutes through a liquid,
with the result being a gradual and com-
OSMOSIS
plete mixing (you can see this mixing when Lipid bilayers are selectively permeable, which means that
tea diffuses through a cup of water, left). some substances can diffuse across them and others can-
Five factors influence diffusion: not (Figure 5.22). The long, nonpolar phospholipid tails
make the core of a bilayer quite hydrophobic (Section 3.3).
Concentration A difference in solute concentration Hydrophobic molecules (such as steroids), as well as gases
(Section 2.4) between adjacent regions of a solution is called and small, uncharged molecules (such as water), can easily
a concentration gradient. Solutes tend to diffuse from a move through this core. However, ions—charged atoms or
region of higher concentration to one of lower concentration; molecules—cannot. Neither can large polar molecules such
the greater the difference in concentration, the faster diffusion as glucose.
occurs. Why? Consider that moving objects (such as mol- When a lipid bilayer separates two fluids with differing
ecules) collide more often as they get more crowded. Thus, solute concentrations, water will diffuse across it. The direc-
during a given interval, more molecules get bumped out of a tion and rate of this diffusion depend on the relative solute
region of higher concentration than get bumped into it. concentration of the two fluids, which we describe in terms
of tonicity. If the solute concentration differs between the two
Temperature Atoms and molecules jiggle faster at higher fluids, the fluid with the lower solute concentration is said to
temperature, so they move more quickly. Thus, diffusion be hypotonic (hypo-, under). The other one, with the higher
occurs more quickly at higher temperatures. solute concentration, is hypertonic (hyper-, over). Water dif-

Size It takes more energy to move a large object than it

does to move a small one, so ions and small molecules diffuse
more quickly than large molecules.

Charge Each ion and charged molecule in a fluid con-

tributes to the fluid’s overall electric charge. A difference in
charge between two regions of the fluid can affect the rate
and direction of diffusion between them. For example, posi-
tively charged ions (such as sodium ions) will tend to diffuse
toward a region with an overall negative charge.
selectively permeable membrane

Pressure Pressure squeezes objects—including atoms and Figure 5.23 Osmosis.

Water moves across a selectively permeable membrane that sepa-
molecules—closer together. Atoms and molecules that are rates two fluids of differing tonicity (red dots represent solutes). The
more crowded collide and rebound more frequently. Thus, volume of fluid in the two compartments changes as water diffuses
diffusion occurs faster at higher pressures. across the membrane between them.

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fuses from a hypotonic fluid into a hypertonic one. The dif-
fusion will continue until the two fluids are isotonic, which 2%
means they have the same overall solute concentration. The sucrose

movement of water across membranes is so important in biol-

ogy that it is given a special name: osmosis (Figure 5.23).
If a cell’s cytoplasm becomes hypertonic with respect to
the fluid outside of its plasma membrane, water will diffuse
into the cell. If the cytoplasm becomes hypotonic, water will
diffuse out. In either case, the solute concentration of the
cytoplasm will change. If it changes enough, the cell’s enzymes 2% sucrose 10% sucrose water
will stop working, with lethal results. Most cells have homeo-
static mechanisms that compensate for osmosis when the A What happens when a semipermeable bag containing a solution
of water and sucrose is immersed in solutions of different tonicities.
solute concentration of cytoplasm differs from extracellular
(external) fluid. In cells with no such mechanism, the vol-
ume—and solute concentration—of cytoplasm changes when B Red blood cells in an iso-
water diffuses into or out of the cell (Figure 5.24). tonic solution (such as the
fluid portion of blood) have
an indented disk shape.
TURGOR
The rigid cell walls of plants and many protists, fungi, and
C Red blood cells immersed
bacteria can resist an increase in the volume of cytoplasm in a hypertonic solution
even in hypotonic environments. Plant cells usually contain shrivel up because water dif-
more solutes than soil water. Thus, water usually diffuses fuses out of them.
from soil into a plant—but only up to a point. Stiff walls
keep plant cells from expanding very much, so an inflow of
D Red blood cells
water causes pressure to build up inside them. Pressure that immersed in a hypotonic
a fluid exerts against a structure that contains it is called solution swell up because
turgor. When enough pressure builds up inside a plant cell, water diffuses into them.
water stops diffusing into it. The amount of turgor that is Some of these have burst.
2 µm
enough to stop osmosis is called osmotic pressure.
Osmotic pressure keeps walled cells plump, just as high Figure 5.24 Effects of tonicity. Like a semipermeable bag filled
air pressure inside a tire keeps it inflated. A young plant can with a solution of sucrose and water (A), red blood cells have no
mechanism to compensate for differences in solute concentration
resist gravity to stay erect because turgor in its cells is high across their membrane (B –D).

?
(Figure 5.25A). If the plant does not get enough water to
replace what it uses, the cytoplasm of its cells shrinks (Figure FIGURE IT OUT
5.25B). As turgor inside the cells decreases, the plant wilts. Which of the three solutions in A is hypotonic with
respect to the fluid in the bag?
Answer: Water

diffusion (dif-YOU-zhun) Spontaneous spreading of molecules or

atoms through a fluid or gas. A Osmotic pressure keeps
hypertonic Describes a fluid that has a high overall solute plant parts erect. These cells
concentration relative to another fluid. in an iris petal are plump
hypotonic Describes a fluid that has a low overall solute with cytoplasm.
concentration relative to another fluid.
isotonic Describes two fluids with identical solute concentrations.
osmosis (oz-MOE-sis) Diffusion of water across a selectively B Cells from a wilted iris
permeable membrane; occurs in response to a difference in solute petal. The cytoplasm shrank,
concentration between the fluids on either side of the membrane. and the plasma membrane
osmotic pressure (oz-MAH-tick) Amount of turgor that prevents moved away from the wall.
osmosis into cytoplasm or other hypertonic fluid.
turgor (TRR-grr) Pressure that a fluid exerts against a structure that
contains it. Figure 5.25 Turgor, as illustrated in cells of iris petals.

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 5.7 Membrane Transport Mechanisms
LEARNI NG OBJ ECTI VES
Extracellular Fluid
Give some important reasons why a cell has to have transport proteins
in its plasma membrane.
Explain how transport proteins selectively move molecules across
membranes, and give an example.
Using appropriate examples, distinguish between passive transport and
facilitated diffusion.
Explain why active transport requires an energy input and passive transport
does not.

Cytoplasm
TRANSPORT PROTEIN SPECIFICITY
Substances that do not diffuse directly through lipid bilay- A A glucose molecule (here, in extracellular fluid) binds to a glucose
ers can cross a cell membrane only through transport pro- transporter (gray) in the plasma membrane.
teins embedded in it (Section 4.3). Each type of transport
protein allows a specific substance to cross: Calcium pumps
pump only calcium ions; glucose transporters transport only
glucose; and so on. This specificity is an important part of
homeostasis. Consider how the composition of cytoplasm
depends on movement of particular solutes across the plasma
membrane, which in turn depends on transport proteins in
the lipid bilayer. Glucose is an important source of energy
for most cells, so they normally take up as much as they can
from extracellular fluid. They do so with the help of glucose
transporters in the plasma membrane. As soon as a molecule
of glucose enters cytoplasm, an enzyme called hexokinase
(shown in Figure 5.9) phosphorylates it. Phosphorylation
traps the molecule inside the cell because the transporters are
B Binding causes the transport protein to change shape.
specific for glucose, not phosphorylated glucose. Thus, phos-
phorylation prevents the molecule from moving back through
the transporter and leaving the cell.

PASSIVE TRANSPORT
Osmosis is an example of passive transport, which is a
membrane-crossing mechanism that requires no energy input.
The diffusion of solutes through transport proteins is another
example. In this case, the movement of the solute and the
direction of its movement are driven entirely by the solute’s
concentration gradient. A few transport proteins form pores
(permanently open channels through a membrane). Gated
transport proteins open and close in response to a stimulus
such as a shift in electric charge or binding to a signaling mol- C The transport protein releases the glucose on the other side of
ecule. Other types change shape upon binding and releasing the membrane (in cytoplasm) and resumes its original shape.
their particular solute.
Figure 5.26 An example of facilitated diffusion.
With a passive transport mechanism called facilitated

?
diffusion, a solute binds to a transport protein, which then
changes shape so the solute is released to the other side of the FIGURE IT OUT
membrane. A glucose transporter is an example of a transport In this example, which fluid is hypotonic: extracellular
fluid or cytoplasm?
Answer: Cytoplasm
protein that works in facilitated diffusion (Figure 5.26).

90 U N I T 1 PRINCIPLES OF CELLULAR LIFE

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 Extracellular Fluid Ca+
Ca+
Ca+ Ca+
Ca+ Ca+ Ca+
Ca+ Ca+
Ca+ Ca+ Ca+ Ca+
Ca+ Ca+ Ca+

Ca+ Ca+

Cytoplasm ATP ADP + Pi

A Two calcium ions (blue) bind to the transport B A phosphate group from ATP causes the pro- C After it loses the calcium ions, the transport
protein (a calcium pump, gray). tein to change shape so that the calcium ions are protein resumes its original shape.
ejected to the opposite side of the membrane.
Figure 5.27 Active transport of calcium ions.

Figure 5.28 The sodium–potassium pump. This protein

(gray) actively transports sodium ions (Na+) from cytoplasm to
Extracellular Fluid
3 4 extracellular fluid, and potassium ions (K+) in the other direc-
tion. ATP provides energy required for transporting both ions
Na+
K+ against their concentration gradient.
Na+
1 2 K+ 5 6 1 Sodium ions in cytoplasm diffuse into the pump’s open chan-
Na+
Na+ nel and bind to its interior.
Na+
K+
2 The transfer of a phosphate group ( P ) from ATP causes the
Na+ pump to change shape so that its channel opens to extracellular
K+
K+
fluid, where it releases the sodium ions 3.
P P
Na+
P
K+ 4 Potassium ions from extracellular fluid diffuse into the chan-
Na+ nel and bind to its interior.
ATP ADP
Na+ 5 The transport protein releases the phosphate group and
reverts to its original shape.
Cytoplasm 6 The channel opens to the cytoplasm, where it releases the
potassium ions.

ACTIVE TRANSPORT
Many cellular processes require transporting solutes across a Consider that calcium ions act as potent messengers
membrane to where their concentration is higher. Moving a that trigger various processes inside cells. The concentration
solute against its concentration gradient requires energy. In of these ions in cytoplasm must be kept thousands of times
active transport, a transport protein uses energy to pump a lower than in extracellular fluid. This gradient is maintained
solute against its gradient across a cell membrane. Typically, by calcium pumps, which export calcium ions from a cell by
an energy input (for example, in the form of a phosphate- active transport (Figure 5.27).
group transfer from ATP) changes the shape of the transport Another example of active transport involves sodium–
protein. The shape change causes the protein to release a potassium pumps. Nearly all of the cells in your body have
bound solute to the other side of the membrane. these proteins, which pump two substances in opposite direc-
tions across the membrane: sodium ions from cytoplasm to
active transport Energy-requiring mechanism in which a extracellular fluid, and potassium ions from extracellular fluid
transport protein pumps a solute across a cell membrane against to cytoplasm (Figure 5.28).
the solute’s concentration gradient. Bear in mind that the membranes of all cells, not just
facilitated diffusion Passive transport mechanism in which a
those of animals, have proteins that carry out active transport.
solute follows its concentration gradient across a membrane by
moving through a transport protein. In plants, for example, transport proteins in the plasma mem-
passive transport Membrane-crossing mechanism that requires branes of photosynthetic cells pump sugar molecules from
no energy input. cytoplasm into tubes that thread throughout the plant body.

C H A P T E R 5 GROUND RULES OF METABOLISM 91

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 5.8 Membrane Trafficking
LEARNI NG OBJ ECTI VES
Identify and explain the process by which cells expel materials in bulk.
Explain how a vesicle forms at the plasma membrane.
Explain the mechanism by which cells sample extracellular fluid.
Describe the way cells take in and digest large particles.

VESICLE MOVEMENT
A Exocytosis. A vesicle in cytoplasm fuses with the plasma mem-
Think back on the fluid mosaic structure of a lipid bilayer brane. Lipids and proteins of the vesicle’s membrane become part of
(Section 4.3). When a membrane is disrupted, the fatty acid the plasma membrane as its contents are expelled to external fluid.
tails of the phospholipids in the bilayer become exposed to
their watery surroundings. Remember, in water, phospholip-
ids spontaneously rearrange themselves so that their nonpolar
tails stay together. Thus, a membrane tends to seal itself after
a disruption. Vesicles form the same way. When a patch of
membrane bulges into the cytoplasm, the hydrophobic tails
of the lipids in the bilayer are repelled by the watery fluid on
both sides. The fluid “pushes” the phospholipid tails together,
which helps round off the bud as a vesicle, and also seals the
rupture in the membrane. B Bulk-phase endocytosis. A pit in the plasma membrane traps
Vesicles are constantly carrying materials to and from molecules, fluid, and particles near the cell’s surface in a vesicle as it
deepens and sinks into the cytoplasm.
a cell’s plasma membrane. This movement requires energy
because it involves motor proteins that drag the vesicles along
cytoskeletal elements. We describe the movement based on
where and how the vesicle originates, and where it goes.
By exocytosis, a vesicle in the cytoplasm moves to the
cell’s surface and fuses with the plasma membrane. As the
fusion occurs, the contents of the vesicle are released to the
surrounding fluid (Figure 5.29A).
There are several pathways of endocytosis, but all take
up substances near the cell’s surface in bulk (as opposed to
one molecule or ion at a time via transport proteins). Cells C Receptor-mediated endocytosis. Receptors on the cell surface
bind a target molecule and trigger a pit to form in the plasma
bring in extracellular fluid by a pathway called bulk-phase membrane. The target molecules are trapped in a vesicle as the pit
endocytosis, in which a patch of plasma membrane balloons deepens and sinks into the cell’s cytoplasm. This mode is more selec-
inward and then pinches off as it sinks into the cytoplasm tive about what is taken into the cell than bulk-phase endocytosis.
(Figure 5.29B). The balloon becomes a vesicle that encloses
a drop of extracellular fluid (along with whatever solutes
endocytic vesicle
and particles are suspended in it). Bulk-phase endocytosis is lipoprotein particle
nonspecific about what it brings into the cell, so it is used for
sampling the composition of extracellular fluid.
In receptor-mediated endocytosis, molecules of a tar-
geted substance trigger endocytosis (Figure 5.29C). Receptor
proteins in the plasma membrane bind to a substance such
as a hormone, or a particle such as a bacterium. The binding
triggers a shallow pit to form in the membrane, just under
the receptors. The pit sinks into the cytoplasm and traps the
targeted molecules in a vesicle as it closes back on itself. LDL D Example of receptor-mediated endocytosis: intake of lipoprotein
and other lipoprotein particles (Section 3.4) enter cells this particles.
way (Figure 5.29D). Figure 5.29 Exocytosis and endocytosis.

92 U N I T 1 PRINCIPLES OF CELLULAR LIFE C R E D I T: (29D) Reprinted from Cell Vol. 10, Richard G. W. Anderson, Michael S. Brown, Joseph L. Goldstein, Role
of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human firoblasts, Pages
351–364, © 1977, with permission from Elsevier.

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Figure 5.30 Phagocytosis. Above, a phagocytic white blood cell’s pseudopods (extending lobes of cytoplasm)
surrounding tuberculosis bacteria (in red). The artwork (right) shows how plasma membrane above the bulg-
ing lobes fuses and forms a vesicle. Once inside the cytoplasm, the endocytic vesicle will fuse with a lysosome.
Lysosomal enzymes will then break down the contents of the vesicle.

Phagocytosis (which means “cell eating”) is a type of target trap it inside an endocytic vesicle that sinks into the
receptor-mediated endocytosis in which mobile cells engulf cytoplasm. Typically, the vesicle merges with a lysosome, and
microorganisms, cellular debris, or other large particles the object taken in by phagocytosis is digested by lysosomal
(Figure 5.30). Many single-celled protists such as amoebas enzymes. The resulting molecular bits may be recycled by the
feed by this pathway. Some of your white blood cells use cell, or expelled by exocytosis.
phagocytosis to engulf viruses, bacteria, cancerous body cells,
and other threats to health.
Phagocytosis begins when receptor proteins bind
MEMBRANE RECYCLING
to a particular extracellular target. The binding causes The composition of a plasma membrane begins in the endo-
microfilaments to assemble in a mesh under the plasma plasmic reticulum (ER). There, membrane proteins and lipids
membrane. The microfilaments then contract, forcing a lobe are made and modified, and both become part of vesicles that
of membrane-enclosed cytoplasm to bulge outward as a transport them to Golgi bodies for final modification (Sec-
pseudopod (Section 4.9). Pseudopods that merge around a tion 4.6). New plasma membrane forms when the finished
proteins and lipids are repackaged as vesicles that travel to the
endocytosis (en-doe-sigh-TOE-sis) Process by which a cell takes plasma membrane and fuse with it.
in a small amount of extracellular fluid (and its contents) by the As long as a cell is alive, exocytosis and endocytosis
ballooning inward of the plasma membrane. continually replace and withdraw patches of its plasma mem-
exocytosis (ex-oh-sigh-TOE-sis) Process by which a cell expels a
brane. If the cell is not enlarging, the total area of the plasma
vesicle’s contents to extracellular fluid.
membrane remains more or less constant because membrane
phagocytosis (fag-oh-sigh-TOE-sis) “Cell eating”; type of
receptor-mediated endocytosis in which a cell engulfs a large solid lost as a result of endocytosis is replaced by membrane arriv-
particle such as another cell. ing as exocytic vesicles.

C R E D I T: (30 left) SPL/Science Source. C H A P T E R 5 GROUND RULES OF METABOLISM 93

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