Lehninger Principles of Biochemistry

1118 Pages·2004·107.76 MB·English

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1
chapter
THE FOUNDATIONS
OF BIOCHEMISTRY
1.1 Cellular Foundations 3 life arose—simple microorganisms with the ability to ex-
tract energy from organic compounds or from sunlight,
1.2 Chemical Foundations 12
which they used to make a vast array of more complex
1.3 Physical Foundations 21
biomoleculesfrom the simple elements and compounds
1.4 Genetic Foundations 28 on the Earth’s surface.
Biochemistry asks how the remarkable properties
1.5 Evolutionary Foundations 31
of living organisms arise from the thousands of differ-
ent lifeless biomolecules. When these molecules are iso-
With the cell,biology discovered its atom...To lated and examined individually, they conform to all the
characterize life,it was henceforth essential to study the physical and chemical laws that describe the behavior
cell and analyze its structure: to single out the common of inanimate matter—as do all the processes occurring
in living organisms. The study of biochemistry shows
denominators,necessary for the life of every cell;
how the collections of inanimate molecules that consti-
alternatively,to identify differences associated with the
tute living organisms interact to maintain and perpetu-
performance of special functions.
ate life animated solely by the physical and chemical
—François Jacob,La logique du vivant: une histoire de l’hérédité laws that govern the nonliving universe.
(The Logic of Life: A History of Heredity),1970 Yet organisms possess extraordinary attributes,
properties that distinguish them from other collections
We must,however,acknowledge,as it seems to me,that of matter. What are these distinguishing features of liv-
ing organisms?
man with all his noble qualities...still bears in his
bodily frame the indelible stamp of his lowly origin. A high degree of chemical complexity and
—Charles Darwin,The Descent of Man,1871 microscopic organization. Thousands of differ-
ent molecules make up a cell’s intricate internal
structures (Fig. 1–1a). Each has its characteristic
F
ifteen to twenty billion years ago, the universe arose sequence of subunits, its unique three-dimensional
as a cataclysmic eruption of hot, energy-rich sub- structure, and its highly specific selection of
atomic particles. Within seconds, the simplest elements binding partners in the cell.
(hydrogen and helium) were formed. As the universe Systems for extracting, transforming, and
expanded and cooled, material condensed under the in- using energy from the environment (Fig.
fluence of gravity to form stars. Some stars became 1–1b), enabling organisms to build and maintain
enormous and then exploded as supernovae, releasing their intricate structures and to do mechanical,
the energy needed to fuse simpler atomic nuclei into the chemical, osmotic, and electrical work. Inanimate
more complex elements. Thus were produced, over bil- matter tends, rather, to decay toward a more
lions of years, the Earth itself and the chemical elements disordered state, to come to equilibrium with its
found on the Earth today. About four billion years ago, surroundings.
1
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2 Chapter 1 The Foundations of Biochemistry
This is true not only of macroscopic structures,
such as leaves and stems or hearts and lungs, but
also of microscopic intracellular structures and indi-
vidual chemical compounds. The interplay among
the chemical components of a living organism is dy-
namic; changes in one component cause coordinat-
ing or compensating changes in another, with the
whole ensemble displaying a character beyond that
of its individual parts. The collection of molecules
carries out a program, the end result of which is
reproduction of the program and self-perpetuation
(a)
of that collection of molecules—in short, life.
A history of evolutionary change. Organisms
change their inherited life strategies to survive
in new circumstances. The result of eons of
evolution is an enormous diversity of life forms,
superficially very different (Fig. 1–2) but
fundamentally related through their shared ancestry.
Despite these common properties, and the funda-
mental unity of life they reveal, very few generalizations
(b) about living organisms are absolutely correct for every
organism under every condition; there is enormous di-
versity. The range of habitats in which organisms live,
from hot springs to Arctic tundra, from animal intestines
to college dormitories, is matched by a correspondingly
wide range of specific biochemical adaptations, achieved
(c)
FIGURE 1–1 Some characteristics of living matter. (a) Microscopic
complexity and organization are apparent in this colorized thin sec-
tion of vertebrate muscle tissue, viewed with the electron microscope.
(b)A prairie falcon acquires nutrients by consuming a smaller bird.
(c)Biological reproduction occurs with near-perfect fidelity.
A capacity for precise self-replication and
self-assembly (Fig. 1–1c). A single bacterial cell
placed in a sterile nutrient medium can give rise
to a billion identical “daughter” cells in 24 hours.
Each cell contains thousands of different molecules,
some extremely complex; yet each bacterium is
a faithful copy of the original, its construction
FIGURE 1–2 Diverse living organisms share common chemical fea-
directed entirely from information contained
tures. Birds, beasts, plants, and soil microorganisms share with hu-
within the genetic material of the original cell.
mans the same basic structural units (cells) and the same kinds of
Mechanisms for sensing and responding to
macromolecules (DNA, RNA, proteins) made up of the same kinds of
alterations in their surroundings, constantly
monomeric subunits (nucleotides, amino acids). They utilize the same
adjusting to these changes by adapting their
pathways for synthesis of cellular components, share the same genetic
internal chemistry.
code, and derive from the same evolutionary ancestors. Shown here
Defined functions for each of their compo- is a detail from “The Garden of Eden,” by Jan van Kessel the Younger
nents and regulated interactions among them. (1626–1679).
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1.1 Cellular Foundations 3
within a common chemical framework. For the sake of Nucleus (eukaryotes)
clarity, in this book we sometimes risk certain general- or nucleoid (bacteria)
Contains genetic material–DNA and
izations, which, though not perfect, remain useful; we
associated proteins. Nucleus is
also frequently point out the exceptions that illuminate membrane-bounded.
scientific generalizations.
Plasma membrane
Biochemistry describes in molecular terms the struc-
Tough, flexible lipid bilayer.
tures, mechanisms, and chemical processes shared by Selectively permeable to
all organisms and provides organizing principles that polar substances. Includes
membrane proteins that
underlie life in all its diverse forms, principles we refer
function in transport,
to collectively as the molecular logic of life. Although in signal reception,
biochemistry provides important insights and practical and as enzymes.
applications in medicine, agriculture, nutrition, and
industry, its ultimate concern is with the wonder of life
itself.
In this introductory chapter, then, we describe
(briefly!) the cellular, chemical, physical (thermody-
namic), and genetic backgrounds to biochemistry and
the overarching principle of evolution—the develop-
ment over generations of the properties of living cells.
Cytoplasm
As you read through the book, you may find it helpful
Aqueous cell contents and
to refer back to this chapter at intervals to refresh your suspended particles
memory of this background material. and organelles.
1.1 Cellular Foundations centrifuge at 150,000 g
The unity and diversity of organisms become apparent Supernatant: cytosol
even at the cellular level. The smallest organisms consist Concentrated solution
of enzymes, RNA,
of single cells and are microscopic. Larger, multicellular
monomeric subunits,
organisms contain many different types of cells, which metabolites,
vary in size, shape, and specialized function. Despite inorganic ions.
these obvious differences, all cells of the simplest and
Pellet: particles and organelles
most complex organisms share certain fundamental
Ribosomes, storage granules,
properties, which can be seen at the biochemical level. mitochondria, chloroplasts, lysosomes,
endoplasmic reticulum.
Cells Are the Structural and Functional Units of All
FIGURE 1–3 The universal features of living cells. All cells have a
Living Organisms
nucleus or nucleoid, a plasma membrane, and cytoplasm. The cytosol
Cells of all kinds share certain structural features (Fig. is defined as that portion of the cytoplasm that remains in the super-
1–3). The plasma membranedefines the periphery of natant after centrifugation of a cell extract at 150,000 g for 1 hour.
the cell, separating its contents from the surroundings.
It is composed of lipid and protein molecules that form The internal volume bounded by the plasma mem-
a thin, tough, pliable, hydrophobic barrier around the brane, the cytoplasm (Fig. 1–3), is composed of an
cell. The membrane is a barrier to the free passage of aqueous solution, the cytosol, and a variety of sus-
inorganic ions and most other charged or polar com- pended particles with specific functions. The cytosol is
pounds. Transport proteins in the plasma membrane al- a highly concentrated solution containing enzymes and
low the passage of certain ions and molecules; receptor the RNA molecules that encode them; the components
proteins transmit signals into the cell; and membrane (amino acids and nucleotides) from which these macro-
enzymes participate in some reaction pathways. Be- molecules are assembled; hundreds of small organic
cause the individual lipids and proteins of the plasma molecules called metabolites,intermediates in biosyn-
membrane are not covalently linked, the entire struc- thetic and degradative pathways; coenzymes, com-
ture is remarkably flexible, allowing changes in the pounds essential to many enzyme-catalyzed reactions;
shape and size of the cell. As a cell grows, newly made inorganic ions; and ribosomes, small particles (com-
lipid and protein molecules are inserted into its plasma posed of protein and RNA molecules) that are the sites
membrane; cell division produces two cells, each with its of protein synthesis.
own membrane. This growth and cell division (fission) All cells have, for at least some part of their life, ei-
occurs without loss of membrane integrity. ther a nucleus or a nucleoid, in which the genome—
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4 Chapter 1 The Foundations of Biochemistry
the complete set of genes, composed of DNA—is stored molecular oxygen by diffusion from the surrounding
and replicated. The nucleoid, in bacteria, is not sepa- medium through its plasma membrane. The cell is so
rated from the cytoplasm by a membrane; the nucleus, small, and the ratio of its surface area to its volume is
in higher organisms, consists of nuclear material en- so large, that every part of its cytoplasm is easily reached
closed within a double membrane, the nuclear envelope. by O diffusing into the cell. As cell size increases, how-
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Cells with nuclear envelopes are called eukaryotes ever, surface-to-volume ratio decreases, until metabo-
(Greek eu, “true,” and karyon, “nucleus”); those with- lism consumes O faster than diffusion can supply it.
2
out nuclear envelopes—bacterial cells—are prokary- Metabolism that requires O thus becomes impossible
2
otes (Greek pro, “before”). as cell size increases beyond a certain point, placing a
theoretical upper limit on the size of the cell.
Cellular Dimensions Are Limited by Oxygen Diffusion
There Are Three Distinct Domains of Life
Most cells are microscopic, invisible to the unaided eye.
Animal and plant cells are typically 5 to 100 (cid:1)m in di- All living organisms fall into one of three large groups
ameter, and many bacteria are only 1 to 2 (cid:1)m long (see (kingdoms, or domains) that define three branches of
the inside back cover for information on units and their evolution from a common progenitor (Fig. 1–4). Two
abbreviations). What limits the dimensions of a cell? The large groups of prokaryotes can be distinguished on bio-
-
lower limit is probably set by the minimum number of chemical grounds: archaebacteria(Greek arche,“ori-
each type of biomolecule required by the cell. The gin”) and eubacteria (again, from Greek eu, “true”).
smallest cells, certain bacteria known as mycoplasmas, Eubacteria inhabit soils, surface waters, and the tissues
are 300 nm in diameter and have a volume of about of other living or decaying organisms. Most of the well-
10(cid:1)14mL. A single bacterial ribosome is about 20 nm in studied bacteria, including Escherichia coli, are eu-
its longest dimension, so a few ribosomes take up a sub- bacteria. The archaebacteria, more recently discovered,
stantial fraction of the volume in a mycoplasmal cell. are less well characterized biochemically; most inhabit
The upper limit of cell size is probably set by the extreme environments—salt lakes, hot springs, highly
rate of diffusion of solute molecules in aqueous systems. acidic bogs, and the ocean depths. The available evi-
For example, a bacterial cell that depends upon oxygen- dence suggests that the archaebacteria and eubacteria
consuming reactions for energy production must obtain diverged early in evolution and constitute two separate
Eubacteria Eukaryotes
Animals Ciliates
Gram- Green Fungi
positive nonsulfur Plants
Purple bacteria bacteria bacteria
Flagellates
Cyanobacteria
Flavobacteria
Microsporidia
Thermotoga
Extreme
halophiles
Methanogens Extreme thermophiles
Archaebacteria
FIGURE 1–4 Phylogeny of the three domains of life. Phylogenetic relationships are often illustrated by a “family tree”
of this type. The fewer the branch points between any two organisms, the closer is their evolutionary relationship.
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1.1 Cellular Foundations 5
All organisms
Phototrophs Chemotrophs
(energy from (energy from chemical
light) compounds)
Autotrophs Heterotrophs Heterotrophs
(carbon from (carbon from (carbon from organic
CO2) organic compounds)
compounds)
Examples:
•Cyanobacteria Examples:
•Plants •Purple bacteria
•Green bacteria
Lithotrophs Organotrophs
(energy from (energy from
inorganic organic
compounds) compounds)
Examples: Examples:
•Sulfur bacteria •Most prokaryotes
FIGURE 1–5 Organisms can be classified according to their source •Hydrogen bacteria •All nonphototrophic
of energy (sunlight or oxidizable chemical compounds) and their eukaryotes
source of carbon for the synthesis of cellular material.
domains, sometimes called Archaea and Bacteria. All eu- atoms exclusively from CO (that is, no chemotrophs
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karyotic organisms, which make up the third domain, are autotrophs), but the chemotrophs may be further
Eukarya, evolved from the same branch that gave rise classified according to a different criterion: whether the
to the Archaea; archaebacteria are therefore more fuels they oxidize are inorganic (lithotrophs) or or-
closely related to eukaryotes than to eubacteria. ganic (organotrophs).
Within the domains of Archaea and Bacteria are sub- Most known organisms fall within one of these four
groups distinguished by the habitats in which they live. broad categories—autotrophs or heterotrophs among the
In aerobic habitats with a plentiful supply of oxygen, photosynthesizers, lithotrophs or organotrophs among
some resident organisms derive energy from the trans- the chemical oxidizers. The prokaryotes have several gen-
fer of electrons from fuel molecules to oxygen. Other eral modes of obtaining carbon and energy. Escherichia
environments are anaerobic, virtually devoid of oxy- coli, for example, is a chemoorganoheterotroph; it re-
gen, and microorganisms adapted to these environments quires organic compounds from its environment as fuel
obtain energy by transferring electrons to nitrate (form- and as a source of carbon. Cyanobacteria are photo-
ing N ), sulfate (forming H S), or CO (forming CH ). lithoautotrophs; they use sunlight as an energy source
2 2 2 4
Many organisms that have evolved in anaerobic envi- and convert CO into biomolecules. We humans, like E.
2
ronments are obligate anaerobes: they die when ex- coli, are chemoorganoheterotrophs.
posed to oxygen.
We can classify organisms according to how they
Escherichia coli Is the Most-Studied Prokaryotic Cell
obtain the energy and carbon they need for synthesiz-
ing cellular material (as summarized in Fig. 1–5). There Bacterial cells share certain common structural fea-
are two broad categories based on energy sources: pho- tures, but also show group-specific specializations (Fig.
-
totrophs (Greek trophe, “nourishment”) trap and use 1–6). E. coli is a usually harmless inhabitant of the hu-
sunlight, and chemotrophs derive their energy from man intestinal tract. The E. colicell is about 2 (cid:1)m long
oxidation of a fuel. All chemotrophs require a source of and a little less than 1 (cid:1)m in diameter. It has a protec-
organic nutrients; they cannot fix CO into organic com- tive outer membrane and an inner plasma membrane
2
pounds. The phototrophs can be further divided into that encloses the cytoplasm and the nucleoid. Between
those that can obtain all needed carbon from CO (au- the inner and outer membranes is a thin but strong layer
2
totrophs) and those that require organic nutrients of polymers called peptidoglycans, which gives the cell
(heterotrophs). No chemotroph can get its carbon its shape and rigidity. The plasma membrane and the
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6 Chapter 1 The Foundations of Biochemistry
Ribosomes Bacterial ribosomes are smaller than FIGURE 1–6 Common structural features of bacterial cells.Because
eukaryotic ribosomes, but serve the same function— of differences in the cell envelope structure, some eubacteria (gram-
protein synthesis from an RNA message.
positive bacteria) retain Gram’s stain, and others (gram-negative
bacteria) do not. E. coli is gram-negative. Cyanobacteria are also
Nucleoid Contains a single,
simple, long circular DNA eubacteria but are distinguished by their extensive internal membrane
molecule. system, in which photosynthetic pigments are localized. Although the
cell envelopes of archaebacteria and gram-positive eubacteria look
Pili Provide similar under the electron microscope, the structures of the membrane
points of lipids and the polysaccharides of the cell envelope are distinctly dif-
adhesion to
ferent in these organisms.
surface of
other cells.
Flagella layers outside it constitute the cell envelope. In the
Propel cell Archaea, rigidity is conferred by a different type of poly-
through its
mer (pseudopeptidoglycan). The plasma membranes of
surroundings.
eubacteria consist of a thin bilayer of lipid molecules
penetrated by proteins. Archaebacterial membranes
have a similar architecture, although their lipids differ
strikingly from those of the eubacteria.
The cytoplasm of E. coli contains about 15,000
ribosomes, thousands of copies each of about 1,000
different enzymes, numerous metabolites and cofac-
Cell envelope
Structure varies tors, and a variety of inorganic ions. The nucleoid
with type of contains a single, circular molecule of DNA, and the
bacteria.
cytoplasm (like that of most bacteria) contains one or
more smaller, circular segments of DNA called plas-
mids. In nature, some plasmids confer resistance to
toxins and antibiotics in the environment. In the labo-
ratory, these DNA segments are especially amenable
to experimental manipulation and are extremely use-
ful to molecular geneticists.
Most bacteria (including E. coli) lead existences as
individual cells, but in some bacterial species cells tend
to associate in clusters or filaments, and a few (the
Outer membrane Peptidoglycan layer
myxobacteria, for example) demonstrate simple social
Peptidoglycan layer Inner membrane
behavior.
IInnnneerr mmeemmbbrraannee
Eukaryotic Cells Have a Variety of Membranous
Organelles,Which Can Be Isolated for Study
Gram-negative bacteria Gram-positive bacteria Typical eukaryotic cells (Fig. 1–7) are much larger than
Outer membrane; No outer membrane; prokaryotic cells—commonly 5 to 100 (cid:1)m in diameter,
peptidoglycan layer thicker peptidoglycan layer
with cell volumes a thousand to a million times larger than
those of bacteria. The distinguishing characteristics of
eukaryotes are the nucleus and a variety of membrane-
bounded organelles with specific functions: mitochondria,
endoplasmic reticulum, Golgi complexes, and lysosomes.
Plant cells also contain vacuoles and chloroplasts (Fig.
1–7). Also present in the cytoplasm of many cells are
granules or droplets containing stored nutrients such as
starch and fat.
Cyanobacteria Archaebacteria In a major advance in biochemistry, Albert Claude,
Gram-negative; tougher No outer membrane;
Christian de Duve, and George Palade developed meth-
peptidoglycan layer; peptidoglycan layer outside
ods for separating organelles from the cytosol and from
extensive internal plasma membrane
membrane system with each other—an essential step in isolating biomolecules
photosynthetic pigments and larger cell components and investigating their
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1.1 Cellular Foundations 7
(a) Animal cell
Ribosomes are protein-
synthesizing machines
Peroxisome destroys peroxides
Cytoskeleton supports cell, aids
in movement of organells
Lysosome degrades intracellular
debris
Transport vesicle shuttles lipids
and proteins between ER, Golgi,
and plasma membrane
Golgi complex processes,
packages, and targets proteins to
other organelles or for export
Smooth endoplasmic reticulum
(SER) is site of lipid synthesis
and drug metabolism
Nuclear envelope segregates Nucleolus is site of ribosomal
chromatin (DNA (cid:1) protein) RNA synthesis
from cytoplasm Nucleus contains the
Rough endoplasmic reticulum
genes (chromatin)
(RER) is site of much protein
synthesis
Plasma membrane separates cell
from environment, regulates
movement of materials into and Ribosomes Cytoskeleton
out of cell
Mitochondrion oxidizes fuels to
produce ATP
Golgi
complex
Chloroplast harvests sunlight,
produces ATP and carbohydrates
Starch granule temporarily stores
carbohydrate products of
photosynthesis
Thylakoids are site of light-
driven ATP synthesis
Cell wall provides shape and
rigidity; protects cell from
osmotic swelling
Vacuole degrades and recycles
macromolecules, stores
metabolites
Cell wall of adjacent cell
Plasmodesma provides path
between two plant cells
Glyoxysome contains enzymes of
the glyoxylate cycle
FIGURE 1–7 Eukaryotic cell structure.Schematic illustrations of the (b) Plant cell
two major types of eukaryotic cell: (a)a representative animal cell
and (b)a representative plant cell. Plant cells are usually 10 to
100(cid:1)m in diameter—larger than animal cells, which typically
range from 5 to 30 (cid:1)m. Structures labeled in red are unique to
either animal or plant cells.
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8 Chapter 1 The Foundations of Biochemistry
structures and functions. In a typical cell fractionation Differential centrifugation results in a rough fraction-
(Fig. 1–8), cells or tissues in solution are disrupted by ation of the cytoplasmic contents, which may be further
gentle homogenization. This treatment ruptures the purified by isopycnic (“same density”) centrifugation. In
plasma membrane but leaves most of the organelles in- this procedure, organelles of different buoyant densities
tact. The homogenate is then centrifuged; organelles (the result of different ratios of lipid and protein in each
such as nuclei, mitochondria, and lysosomes differ in type of organelle) are separated on a density gradient. By
size and therefore sediment at different rates. They also carefully removing material from each region of the gra-
differ in specific gravity, and they “float” at different dient and observing it with a microscope, the biochemist
levels in a density gradient. can establish the sedimentation position of each organelle
FIGURE 1–8 Subcellular fractionation of tissue.A tissue such as liver
is first mechanically homogenized to break cells and disperse their
contents in an aqueous buffer. The sucrose medium has an osmotic
pressure similar to that in organelles, thus preventing diffusion of wa-
ter into the organelles, which would swell and burst. (a)The large and
small particles in the suspension can be separated by centrifugation
at different speeds, or (b) particles of different density can be sepa-
rated by isopycnic centrifugation. In isopycnic centrifugation, a cen-
trifuge tube is filled with a solution, the density of which increases
(a) Differential from top to bottom; a solute such as sucrose is dissolved at different
centrifugation concentrations to produce the density gradient. When a mixture of
❚ organelles is layered on top of the density gradient and the tube is
❚❚ Tissue centrifuged at high speed, individual organelles sediment until their
❚ ❚ homogenization
❚ buoyant density exactly matches that in the gradient. Each layer can
❚❚❚ ❚❚❚❚ ❚ ❚❚❚ L(1o,0w0-0sp ge,e 1d0 c menitnr)ifugation be collected separately.
❚
❚ ❚❚ ❚❚❚❚❚❚▲▲▲▲▲❚❚▲❚❚
❚❚ ❚❚ ❚❚▲❚❚▲▲❚❚❚▲❚❚▲▲❚ ❚ Sm(2u0epd,0ei0urn0ma g-ts,a p2ne0te sdmu cibnejn)etcrtiefdu gtoation (b) I(ssuopcryocsnei-cdensity)
❚❚❚❚▲▲▲❚❚▲▲▲❚❚▲❚❚▲❚❚▲❚❚❚❚ ❚❚❚❚▲❚❚❚❚❚❚▲❚❚ Supernatant subjected centrifugation
homTios❚❚gseune❚a❚te ❚❚❚❚❚▲▲❚❚❚❚▲▲▲❚❚❚❚❚❚❚❚❚❚❚❚▲ tc(8oe 0nh,t0irg0ihf0u- sggpa, et1ei ohdn ) Centrifugation
❚❚
❚ ❚❚▲▲▲▲❚❚ ▲▲❚❚❚❚ ❚❚ ❚❚ Supernatant
❚❚ ❚❚❚❚❚❚❚❚ ▲P▲e▲lle▲t ❚❚❚❚ ❚❚❚❚ svceuenrbytjer hicftiugegdha -tstoipoened
❚❚ ❚❚❚ wchoonleta cienlsls, ❚❚❚❚ ❚❚❚❚ (150,000 g, 3 h)
❚❚❚❚ ❚❚❚❚❚❚❚❚ ❚❚❚❚❚ ❚❚❚❚❚❚❚❚❚❚❚❚❚❚❚❚❚ cymtoepnsmlukabecslrlmeeaitan,oenss, ▲P▲▲e▲▲▲ll❚❚▲e▲t▲
❚❚ ❚❚❚❚ contains Sample
❚ ❚❚ ❚❚ ❚ mitochondria,
❚❚ ❚ ❚❚ ❚❚❚❚ ❚❚❚❚❚ pleyrsooxsiosmomese,s P❚❚❚❚❚❚e❚❚❚❚l❚❚l❚❚e❚❚❚❚❚❚t❚❚ Scspoorunloputtebearilinennsastant Sgruacdrioesnet
❚❚ ❚❚ contains
❚❚❚ ❚❚❚❚ (framgmicernostso mofe EsR), Lcoemssp donenenset
❚ small vesicles Fractionation
More dense
Pellet contains component
ribosomes, large
macromolecules
8 7 6 5 4 3 2 1
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1.1 Cellular Foundations 9
and obtain purified organelles for further study. For into their protein subunits and reassembly into fila-
example, these methods were used to establish that ments. Their locations in cells are not rigidly fixed but
lysosomes contain degradative enzymes, mitochondria may change dramatically with mitosis, cytokinesis,
contain oxidative enzymes, and chloroplasts contain amoeboid motion, or changes in cell shape. The assem-
photosynthetic pigments. The isolation of an organelle en- bly, disassembly, and location of all types of filaments
riched in a certain enzyme is often the first step in the are regulated by other proteins, which serve to link or
purification of that enzyme. bundle the filaments or to move cytoplasmic organelles
along the filaments.
The Cytoplasm Is Organized by the Cytoskeleton The picture that emerges from this brief survey
of cell structure is that of a eukaryotic cell with a
and Is Highly Dynamic
meshwork of structural fibers and a complex system of
Electron microscopy reveals several types of protein fila- membrane-bounded compartments (Fig. 1–7). The fila-
ments crisscrossing the eukaryotic cell, forming an inter- ments disassemble and then reassemble elsewhere. Mem-
locking three-dimensional meshwork, the cytoskeleton. branous vesicles bud from one organelle and fuse with
There are three general types of cytoplasmic filaments— another. Organelles move through the cytoplasm along
actin filaments, microtubules, and intermediate filaments protein filaments, their motion powered by energy de-
(Fig. 1–9)—differing in width (from about 6 to 22 nm), pendent motor proteins. The endomembrane system
composition, and specific function. All types provide segregates specific metabolic processes and provides
structure and organization to the cytoplasm and shape surfaces on which certain enzyme-catalyzed reactions
to the cell. Actin filaments and microtubules also help to occur. Exocytosis and endocytosis, mechanisms of
produce the motion of organelles or of the whole cell. transport (out of and into cells, respectively) that involve
Each type of cytoskeletal component is composed membrane fusion and fission, provide paths between the
of simple protein subunits that polymerize to form fila- cytoplasm and surrounding medium, allowing for secre-
ments of uniform thickness. These filaments are not per- tion of substances produced within the cell and uptake
manent structures; they undergo constant disassembly of extracellular materials.
Actin stress fibers Microtubules Intermediate filaments
(a) (b) (c)
FIGURE 1–9 The three types of cytoskeletal filaments.The upper pan- lin, or intermediate filament proteins are covalently attached to a
els show epithelial cells photographed after treatment with antibodies fluorescent compound. When the cell is viewed with a fluorescence
that bind to and specifically stain (a)actin filaments bundled together microscope, only the stained structures are visible. The lower panels
to form “stress fibers,” (b)microtubules radiating from the cell center, show each type of filament as visualized by (a, b) transmission or
and (c)intermediate filaments extending throughout the cytoplasm. For (c)scanning electron microscopy.
these experiments, antibodies that specifically recognize actin, tubu-
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10 Chapter 1 The Foundations of Biochemistry
Although complex, this organization of the cyto- reversible, and subject to regulation in response to var-
plasm is far from random. The motion and the position- ious intracellular and extracellular signals.
ing of organelles and cytoskeletal elements are under
tight regulation, and at certain stages in a eukaryotic Cells Build Supramolecular Structures
cell’s life, dramatic, finely orchestrated reorganizations,
Macromolecules and their monomeric subunits differ
such as the events of mitosis, occur. The interactions be-
greatly in size (Fig. 1–10). A molecule of alanine is less
tween the cytoskeleton and organelles are noncovalent,
than 0.5 nm long. Hemoglobin, the oxygen-carrying pro-
tein of erythrocytes (red blood cells), consists of nearly
600 amino acid subunits in four long chains, folded into
(a) Some of the amino acids of proteins
globular shapes and associated in a structure 5.5 nm in
diameter. In turn, proteins are much smaller than ribo-
(cid:1) (cid:1) (cid:1)
COO COO COO
somes (about 20 nm in diameter), which are in turn
(cid:2) A (cid:2) A (cid:2) A
H3NOCAOH H3NOCAOH H3NOCAOH much smaller than organelles such as mitochondria, typ-
ically 1,000 nm in diameter. It is a long jump from sim-
CH CH OH CH
3 2 2
A ple biomolecules to cellular structures that can be seen
(cid:1)
Alanine Serine COO
Aspartate
(cid:1) (cid:1)
COO COO
(cid:2) A (cid:2) A COO(cid:1) FIGURE 1–10 The organic compounds from which most cellular
H3NOCAOH H3NOCAOH (cid:2) A materials are constructed: the ABCs of biochemistry.Shown here are
H NOCOH
CH2 CAH2 3 A (a) six of the 20 amino acids from which all proteins are built (the
C NH CH2 side chains are shaded pink); (b)the five nitrogenous bases, two five-
A
CH SH carbon sugars, and phosphoric acid from which all nucleic acids are
HC (cid:2)
NH built; (c)five components of membrane lipids; and (d)D-glucose, the
Cysteine
parent sugar from which most carbohydrates are derived. Note that
OH
Histidine
phosphoric acid is a component of both nucleic acids and membrane
Tyrosine
lipids.
(b) The components of nucleic acids (c) Some components of lipids
O O NH COO(cid:1) COO(cid:1) CH2OH
2
C C CH CH CH CHOH
HN CH HN C 3 N CH 2 2
CH CH CH OH
2 2 2
C CH C CH C CH
O N O N O N CH2 CH2 Glycerol
H H H
CH CH
Uracil Thymine Cytosine 2 2 CH
3
CH2 CH2 CH (cid:2)N CH CH OH
3 2 2
NH2 O CH2 CH2 CH
3
C N C N O(cid:1) CH2 CH2 Choline
N C HN C
CH CH
CH CH HO P OH 2
HC C C C
N N H N N N O CH CH2
H 2 H
Phosphoric acid CH CH
2 2
Adenine Guanine CH CH (d) The parent sugar
Nitrogenous bases 2 2
CH CH
2 2
HOCH2 O H HOCH2 O H CH2 CH2 CH2OH
O
H H H H CH2 CH2 H H
H OH H OH H
CH2 CH3 OH H
OH OH OH H CH Palmitate HO OH
2
(cid:3) -D-Ribose 2-Deoxy-(cid:3) -D-ribose CH3 H OH
Five-carbon sugars Oleate (cid:3) -D-Glucose