Wonder Drug j What You Will Be Learning
3.1 How Penicillin Was Discovered
3.2 Cell Theory: All Living Things Are Made of Cells
3.3 Membranes: All Cells Have Them
3.4 Prokaryotic and Eukaryotic Cells Have
Different Structures
3.5 Some Antibiotics Target Bacterial Cell Walls
3.6 Some Antibiotics Inhibit Prokaryotic
Ribosomes
3.7 Molecules Move across the Cell Membrane
3.8 Eukaryotic Cells Have Organelles
UP CLOSE Eukaryotic Organelles
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Chapter 3 Cell Function and Structure
Wonder Drug
How a chance discovery in a London laboratory revolutionized medicine
O
n a September morning in 1928, biologist Alexander Fleming returned to his laboratory at St. Mary’s Hospital in
London after a short summer vacation. As usual, the place was a mess—his bench piled high with the petri dishes on which he was growing bacteria. On this day, as Fleming sorted through the plates, he noticed that one was growing a patch of fluffy white mold. It had been contaminated, likely by a rogue mold spore that had drifted in from a neighboring laboratory. Fleming was about to toss the plate in the sink when he noticed something unusual: wherever mold was growing, there was a zone around the mold where the bacteria did not seem to grow.
Curious, he looked under a microscope and saw that the bacterial cells near the mold had burst, or lysed. Something in the mold was killing the bacteria. Experiments confirmed that the mold was capable of killing many kinds of bacteria,
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in luding Streptococcus, Staphylococcus, and c Pneumococcus. Fleming published his results in 1929 in the British Journal of Experimental
Pathology. He named the antibacterial substance “penicillin,” after the fungus producing it, Penicillium notatum. It was the birth of the first antibiotic.
Fleming was not the first to notice the bacteria-killing property of Penicillium, but he was the first to study it scientifically and publish the results. In fact, Fleming had been looking for bacteria-killing substances for a number of years, ever since he had served as a medical officer in World War I and witnessed soldiers dying from bacteria-caused infections. He had already discovered one such antimicrobial agent—the chemical lysozyme—which he detected in his own tears and nasal mucus, so he knew what bacteria-killing signs to look for.
If you’ve ever seen a piece of moldy bread or rotting fruit, then you’ve met the Penicillium fungus. It doesn’t look very impressive, but the
ANTIBIOTIC
A chemical that can slow or stop the growth of bacteria; many antibiotics are produced by living organisms. UNIT 1: WHAT IS LIFE MADE OF? CHEMISTRY, CELLS, ENERGY
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Fleming in his lab.
CELL THEORY
The concept that all living organisms are made of cells and that cells are formed by the reproduction of existing cells.
chemical it produces ushered in a whole new age of medicine. For the first time, doctors had a way to treat such deadly illnesses as bacterial pneumonia, syphilis, and meningitis. As physician Lewis Thomas, former president of
Memorial Sloan-Kettering Cancer Center in
New York City, wrote in his 1992 memoir Fragile Species, “We could hardly believe our eyes on seeing that bacteria could be killed off without at the same time killing the patient. It was not just amazement, it was a revolution” (Infographic 3.1).
Bug Bullet
What makes antibiotics special is not just their ability to kill bacteria. After all, cyanide and soap kill bacteria just fine. The important thing about antibiotics is that they exert their
destructive effects on bacteria without harming their human or animal host, even if taken internally. “We could hardly believe our eyes on seeing that bacteria could be killed off without at the same time killing the patient. It was not just amazement, it was a revolution.” –Lewis Thomas
Although Fleming didn’t know it at the time, penicillin and other antibiotics preferentially kill bacteria because they target what is unique about bacterial cells. According to the cell theory, all living things are made of cells, and
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INFOGRAPHIC 3.1
How Penicillin Was Discovered
A fortuitous observation by
Fleming led to the discovery of the first antibiotic. He realized that the fungus on his culture plate was somehow inhibiting the reproduction of bacteria.
A single bacterial cell lands on a culture plate far away from the mold.
Nutrients in the plate support the growth and division of the bacterial cells.
After many rounds of cell division, enough cells accumulate in this spot to be visualized as a colony on the plate.
Staphylococcus bacterial colonies form at locations far away from the mold.
Bacterial colonies are unable to form near the mold.
Penicillium under a microscope and on an orange
Penicillium mold
Penicillium mold
Figure 2 from Alexander Fleming’s 1929 paper, showing the response of different bacteria to penicillin. 42
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every new cell comes from the division of a pre-existing one. But not all cells are alike.
Cells come in many shapes and sizes and perform various functions, depending on where they are found (Infographic 3.2). Moreover, they fall into two fundamentally different categories: prokaryotic or eukaryotic. Prokaryotic cells are relatively small and lack internal membrane-bound compartments, called organelles. Eukaryotic cells, by contrast, are much larger and contain many such organelles. Penicillin and other antibiotics target structures that are unique to prokaryotic cells.
To understand why antibiotics affect prokaryotic and eukaryotic cells differently, it helps
PROKARYOTIC
CELLS
Cells that lack internal membrane-bound organelles.
EUKARYOTIC CELLS
Cells that contain membrane-bound organelles, including a central nucleus.
ORGANELLES
The membrane-bound compartments of eukaryotic cells that carry out specific functions. UNIT 1: WHAT IS LIFE MADE OF? CHEMISTRY, CELLS, ENERGY
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INFOGRAPHIC 3.2
Cell Theory: All Living Things Are Made of Cells
All living organisms are composed of cells. These cells arise from the reproduction of existing cells.
Different cells have different structures and functions.
Diatoms: single-cell eukaryotes
Amoeba (a protozoan): a single-cell eukaryote
Bacteria: single-cell prokaryotes
Molds (fungi): single and multicellular eukaryotic cells
Elodea (an aquatic plant): a multicellular eukaryote
Humans (these are heart cells): multicellular eukaryotes
CELL MEMBRANE
A phospholipid bilayer with embedded proteins that forms the boundary of all cells. CYTOPLASM
The gelatinous, aqueous interior of all cells. RIBOSOME
A complex of RNA and protein that carries out protein synthesis in all cells.
NUCLEUS
The organelle in eukaryotic cells that contains the genetic material. to understand first what the two cell types have in common. All cells, both prokaryotic and eukaryotic, are surrounded by a cell membrane.
This f lexible yet sturdy structure forms a boundary between the external environment and the cell’s watery cytoplasm and literally holds the cell together. Partly hydrophobic, partly hydrophilic molecules known as phospholipids make up the bulk of the cell membrane, and proteins embedded in the membrane perform particular functions, such as transporting nutrients in and wastes out.
The cell membrane forms a semipermeable barrier to substances on either side of it (Infographic 3.3).
In addition to a f lexible cell membrane, both prokaryotic and eukaryotic cells have two
other elements in common: ribosomes, which synthesize the proteins that are crucial to cell function; and DNA, the molecule of heredity. Beyond these three features, however—cell membrane, ribosomes, and DNA—the two cell types are structurally quite different. In a prokaryotic cell, for instance, the DNA floats freely within the cell’s cytoplasm, while in a eukaryotic cell it is housed within a central command center called the nucleus. The nucleus is one of many organelles found within eukaryotic cells, but not in their simpler prokaryotic cousins (Infographic 3.4).
Penicillin kills bacteria because of one im portant difference between prokaryotic and eukaryotic cells. Unlike human and other ani-
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mal cells, most bacteria are surrounded by a cell wall. This rigid structure is what allows bacteria to survive in watery environments— say, your intestines or a pond.
Water has a tendency to move across cell membranes from lower to higher solute concentration, a process called osmosis. In a lowsolute environment, water will tend to rush into the solute-rich cytoplasm of a cell, causing it to swell. This swelling is potentially fatal to bacteria. Without a cell wall, bacterial cells would fill up with water and burst. Their sturdy
cell wall, however, counteracts this osmotic pressure, keeping too much water from rushing in. (Eukaryotic cells are protected from osmotic pressure by the cholesterol in their cell membrane.)
What makes the bacterial cell wall rigid is the molecule peptidoglycan, a polymer made of sugars and amino acids that link to form a chainlike sheath around the cell. Different bacterial walls can have different structures, but all have peptidoglycan, which is found only in bacteria. By interfering with the synthesis of
CELL WALL
A rigid structure enclosing the cell membrane of some cells that helps the cell maintain its shape. INFOGRAPHIC 3.3
Membranes: All Cells Have Them
Phospholipid
CH3
H 2C
Hydrophilic head CH2 CH3
O
O
P
O
H 2C
CH CH2
O
Hydrophilic tail N+ CH3
C
O
O
C
O–
Choline group Phosphate group Membranes that form the cell membrane and various organelles are phospholipid bilayers with embedded and attached proteins. Membranes are semipermeable, selectively allowing the passage of substances from one side to the other.
Phospholipids form two layers when there is water on two sides — outside the cell and in the cytoplasm.
Hydrophilic heads face out to interact with water on both sides.
Glycerol
O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
Cell membrane
HC
CH2
CH
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH3
Hydrophobic tails gather in the middle of the membrane.
Membrane proteins Fatty acid
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INFOGRAPHIC 3.4
Prokaryotic and Eukaryotic Cells Have Different Structures
While all cells have a cell membrane, cytoplasm, ribosomes and DNA, there are specific structural differences between prokaryotic and eukaryotic cells. Eukaryotic cells contain a variety of membrane-enclosed organelles while prokaryotic cells do not.
Basic Prokaryotic Cell
Basic Eukaryotic Cell
Prokaryotic and eukaryotic cells share these common structures:
Nucleus
Cell membrane
Cytoplasm
Ribosomes
Genetic material
(DNA)
Prokaryotic cells have a cell wall.
Eukaryotic cells have specialized compartments
(organelles) for specific cell functions.
OSMOSIS
The diffusion of water across a semipermeable membrane from an area of lower solute concentration to an area of higher solute concentration. PEPTIDOGLYCAN
A macromolecule that forms all bacterial cell walls and provides rigidity to the cell wall.
Scanning electron micrograph of the bacteria that cause gonorrhea.
peptidoglycan, penicillin weakens the cell wall, which is then no longer able to counteract osmotic water pressure. Eventually, the cell bursts (Infographic 3.5).
Bacteria are not the only organisms with a cell wall (plant cells and certain fungi have them, too), but they are the only ones that have a cell wall made of peptidoglycan—which is why penicillin is such a selective bacteria killer.
Ironically, despite its remarkable killing powers, penicillin was not immediately recognized as a medical breakthrough when it was first discovered. In fact, Fleming didn’t think his mold had much of a future in medicine. At the time, the idea that an antiseptic agent could kill bacteria without at the same time harming the patient was unheard of, so Fleming never considered that penicillin might be taken internally. Nor was he a chemist, so he lacked the expertise to isolate and purify the active ingredient from the mold. While he found that his
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INFOGRAPHIC 3.5
Some Antibiotics Target Bacterial Cell Walls
Penicillin and related antibiotics target the peptidoglycan of bacterial cell walls.
In the absence of antibiotic:
The cell lives:
Most bacterial cells have a rigid cell wall that surrounds the cell membrane. The cell wall helps keep the cells intact, despite the flow of water into the cells.
The peptidoglycan cell wall resists the pressure of the water entering by osmosis. The cell retains its shape.
More solute molecules inside the cell
Cell membrane Peptidoglycan cell wall
Fewer solute molecules outside the cell
Water moves into the cell by osmosis.
Antibiotic
In the presence of antibiotic:
The cell lyses:
When bacterial cells grow in the presence of penicillin, the antibiotic interferes with the synthesis of new cell wall material, resulting in a weak wall.
mold juice made a “reasonably good” topical antiseptic, he noted in a 1940 paper that “the trouble of making it seemed not worth while,” and largely gave up working on it.
Ten years would pass before anyone reconsidered Fleming’s mold. By then, history had intervened and given new urgency to the search for antibacterial medicines. On September 1, 1939, Germany invaded Poland, plunging the world into war for the second time in a generation. With the horrors of World
War I still seared into memory, many feared the
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death toll that would result from the hostilities. Millions of soldiers and civilians had died in World
War I, many not as a result of direct combat injuries but from infections resulting from surgeries meant to treat those injuries.
With few other antibacterial medicines available, penicillin suddenly became the focus of research during World War II.
In 1938, Ernst Chain, a GermanJewish biochemist, was working in the pathology department at Oxford University, having fled Germany for England in 1933 when the Nazis came to power. Both Chain and his supervisor, Howard
Florey, were interested in the biochemistry of antibacterial substances. Chain stumbled across
With few other antibacterial medicines available, penicillin suddenly became the focus of research during
World War II.
From Fungus to Pharmaceutical
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Without a strong wall, the force of water entering the cell is enough to cause the cell to rupture.
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Manufacturing penicillin in 1943: culture flasks are filled with the nutrient solution in which penicillin mold is grown.
Fleming’s 1929 paper on penicillin and set about trying to isolate and concentrate the active ingredient from the mold, which he succeeded in doing by 1940. Chain’s breakthrough allowed Florey’s group to begin testing the drug’s clinical efficacy.
They injected the purified chemical into bacteriainfected mice and found that the mice were quickly rid of their infection. Human trials followed next, in 1941, with the same remarkable result. As encouraging as these results were, there was one nagging problem: it took up to 2,000
liters of mold fluid to obtain enough pure penicillin to treat one person. The Oxford doctors used almost their whole supply of the drug treating their first patient, a policeman ravaged by a staphylococcal infection. The team stepped up their purification efforts—even culturing the mold in patients’ bedpans and re-purifying the drug from patients’ urine—but there was no way they could keep up with demand.
The turning point came in 1941, when Oxford scientists approached the U.S. government and asked for help in growing penicillin on a large scale. The method they devised took advantage of something the United States had in abundance: corn. Using a by-product of large-scale corn processing as a culture medium in which to grow the fungus, the scientists were able to produce penicillin in much greater quantities.
At first, all the penicillin harvested from U.S. production plants came from Fleming’s original strain of Penicillium notatum. But researchers continued to look for more potent strains to improve yields. In 1943, they got lucky: researcher Mary Hunt discovered one such strain growing on a ripe cantaloupe in a Peoria, Illinois, supermarket. This new strain, called
Penicillium chrysogenum, produced more than
200 times the amount of penicillin as the origi-
“For the first time in human history, most people felt that infectious disease was ceasing to be a threat.”
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nal strain. With it, production of the drug soared. By the time the Allies invaded France on June 6, 1944—D-day—they had enough penicillin to treat every soldier that needed it. By the following year, penicillin was widely available to the general public.
“Penicillin seemed to justify a carefree attitude to infection,” says medical historian Robert Bud, principal curator of the Science
Museum in London. “In western countries, for the first time in human history, most people felt that infectious disease was ceasing to be a threat, and sexually infectious disease had already been conquered. For many it seemed cure would be easier than prevention.”
Yet, as effective as penicillin was, it was effective only against certain types of bacteria; against others, it was powerless.
Stockpiling the Antibiotic Arsenal
As Fleming knew, most of the bacterial world falls into one of two categories, Gram-positive and Gram-negative; these names reflect the way bacterial cell walls trap a dye known as
Gram stain (after its discoverer, the Danish scientist Hans Christian Gram). Fleming found that while penicillin easily killed Gram-positive bacteria like Staphylococcus and Streptococcus, it had little effect on Gram-negative bacteria like E. coli and Salmonella, whose cell walls have an extra layer of lipids surrounding them. This extra lipid layer prevents penicillin from reaching the peptidoglycan beneath it.
The discovery that penicillin was effective only on Gram-positive bacteria led other researchers in the 1940s to look for other antibiotics that could kill Gram-negative bacteria. The first such broad-spectrum antibiotic was streptomycin, discovered in 1943 by Albert Schatz and Selman Waksman at Rutgers University. In addition to killing Gram-negative bacteria, streptomycin was the first effective treatment for the deadly bacterial disease tuberculosis.
Like other antibiotics in the class known as aminoglycosides, streptomycin works by interfering with protein synthesis on bacterial ribosomes. Ribosomes are the molecular machines that assemble a cell’s proteins. While both eu-
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karyotic and prokaryotic cells have ribosomes, their ribosomes are different sizes and have different structures. Because streptomycin targets features specific to bacterial ribosomes, it doesn’t harm the human who is taking it (Infographic 3.6).
Antibiotics can also target bacteria by inhibiting a bacterium’s ability to make a critical vitamin or to copy its DNA before dividing. When this happens, the bacterium dies instead of reproducing. “Penicillin seemed to justify a carefree attitude to infection. . . . For many it seemed cure would be easier than prevention.” –Robert Bud
Why can broad-spectrum antibiotics, like streptomycin or gentamicin, kill Gram-negative bacteria when penicillin cannot? It’s because these drugs have a chemical structure that allows them to pass more easily through the outer lipid layer of the Gram-negative bacterial cell wall. Although natural penicillin cannot pass this layer, many modern synthetic varieties of penicillin, known collectively as beta-lactams, can.
Crossing Enemy Lines
For any drug to be effective, it has to reach its designated target. In the case of many antibiotics, that means getting inside the cell to do their work. How do antibiotics penetrate a cell’s outer defenses? In all cells, the cell membrane acts as a barrier to transport, allowing only certain substances to pass through it.
With its densely packed collection of hydrophobic phospholipid tails, the cell membrane prevents many large molecules, like glucose, and hydrophilic substances, like sodium ions, from wandering across the cell membrane. In fact, the only things that do cross the membrane easily are small, uncharged molecules like oxygen (O2), which can travel relatively easily across by a process known as simple diffusion.
Simple diffusion takes advantage of the natural tendency of dissolved substances to spread
GRAM-POSITIVE
Refers to bacteria with a cell wall that includes a thick layer of peptidoglycan that retains the Gram stain. GRAM-NEGATIVE
Refers to bacteria with a cell wall that includes a thin layer of peptidoglycan surrounded by an outer lipid membrane that does not retain the Gram stain.
SIMPLE DIFFUSION
The movement of small, hydrophobic molecules across a membrane from an area of higher concentration to an area of lower concentration; simple diffusion does not require energy.
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INFOGRAPHIC 3.6
Some Antibiotics Inhibit Prokaryotic Ribosomes
Ribosomes are responsible for the synthesis of proteins in both prokaryotic and eukaryotic cells, but their structure is slightly different in the two types of cells. Antibiotics that interfere with prokaryotic ribosomes leave eukaryotic ribosomes unaffected.
Prokaryotic Ribosome:
Antibiotic disrupts ribosome function.
Genetic instructions from the nucleus enter the ribosome.
O
C
OH
C
O
P C
No protein formed
OH
C
Antibiotics interfere with bacterial ribosomes. Protein synthesis is interrupted.
OH
O
P C
C
O
P C
C
Bacterial ribosome
Eukaryotic Ribosome:
Antibiotic does not affect the ribosome.
Genetic instructions from the nucleus enter the ribosome.
Antibiotic
Using these instructions, a new protein chain is formed.
Functional protein
O
C
OH
C
O
P C
OH
OH
C
O
P C
C
O
P C
C
Human ribosome
TRANSPORT
PROTEINS
Proteins involved in the movement of molecules across the cell membrane.
FACILITATED
DIFFUSION
The process by which large or hydrophilic solutes move across a membrane from an area of higher concentration to an area of lower concentration with the help of transport proteins. out from an area of higher concentration to one of lower concentration—think of food coloring diffusing in a glass of water. Because the substance is moving from the side of the membrane with a higher concentration to the side with a lower concentration, no energy is required to move substances across the membrane. Take oxygen, for example. The concentration of oxygen molecules, which are small and uncharged, is often higher outside the cell and lower inside.
This concentration difference, or gradient, allows oxygen to diffuse easily into the cell—a good thing, because the cell needs oxygen in order to survive.
But the cell also needs some large or hydrophilic molecules in order to survive—one of them is glucose, the cell’s energy source. To move such molecules across the membrane the cell makes use of transport proteins. Transport proteins sit in the membrane bilayer with
Eukaryotic ribosomes are unaffected by antibiotic.
Proteins are still produced.
one of their ends outside the cell and the other inside. By acting as a kind of channel, carrier, or pump, transport proteins provide a passageway for those large or hydrophilic molecules to cross the membrane. They are also very specific: a protein that transports glucose will not transport calcium ions, for example. The cells of your body contain hundreds of types of transport proteins.
Some antibiotics are small hydrophobic molecules that can cross the cell membrane directly by simple diffusion—tetracycline, for example.
Others, including penicillin and streptomycin, require the assistance of transport proteins.
Transport proteins can move substances either up or down a concentration gradient. When a substance uses a transport protein to move down a concentration gradient, the process is called facilitated diffusion. Like simple diffusion, facilitated diffusion requires no energy
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INFOGRAPHIC 3.7
Molecules Move across the Cell Membrane
Simple diffusion
Small, uncharged molecules cross the phospholipid bilayer from the side with the higher concentration to the side with the lower concentration without the help of membrane proteins.
Facilitated diffusion
Large or hydrophilic molecules cross the membrane from the side with the higher concentration to the side with the lower concentration with the help of a membrane protein specific for the molecule being transported.
Active transport
Large or hydrophilic molecules cross the membrane from the side with the lower concentration to the side with the higher concentration. Movement requires a specific membrane protein and energy to pump molecules against the gradient.
Higher concentration
Transport proteins Energy
Lower concentration
since the substance is moving from a higher to a lower concentration. Facilitated diffusion is the way many antibiotics pass through bacterial cell membranes.
Just because an antibiotic makes it inside a bacterial cell, however, doesn’t mean it will stay there. Some bacteria have transport proteins that can actively pump the antibiotic back out of the cell. This bacterial counteroffensive measure is an example of active transport, in which proteins pump a substance uphill from an area of lower concentration to an area of higher concentration, a process that requires energy. In this case, active transport keeps the antibiotic concentration in the bacterial cell low, but the cell must expend energy to keep pumping the antibiotic out (Infographic 3.7).
Pumping antibiotics out of the bacterial cell is one way bacteria can resist the destructive power of an antibiotic. Other ways include chemically
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breaking down the antibiotic with enzymes. Why would bacteria have such built-in mechanisms for counteracting or resisting drugs? Remember that penicillin was originally isolated from a living organism, a fungus. Streptomycin was originally isolated from microorganisms living in soil.
Microorganisms have evolved chemical defenses as a way to protect themselves from other organisms. In turn, these organisms have evolved countermeasures that give them resistance. Humans thus find themselves embroiled in a battle originally waged solely between microorganisms. We have “amplified a local warfare among microbes in a few grams of soil into a global planetary war between Man and Microbe,” writes
Alexander Tomasz, a microbiologist at the Rockefeller University, in the book Fighting Infection in the 21st Century. In the early 1980s Tomasz helped discover how penicillin works, and is now an expert on antibiotic resistance.
ACTIVE TRANSPORT
The energy-requiring process by which solutes are pumped from an area of lower concentration to an area of higher concentration with the help of transport proteins. UNIT 1: WHAT IS LIFE MADE OF? CHEMISTRY, CELLS, ENERGY
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INFOGRAPHIC 3.8
Eukaryotic Cells Have Organelles
Humans and other animals, as well as plants, fungi, and protists, are eukaryotes—they are made up of eukaryotic cells, containing many organelles. Some organelles are found in all eukaryotic cells; other organelles are found in only a subset of eukaryotes.
Animal Cell
Both animals and plants are eukaryotes. Their cells contain a number of internal organelles.
Plant Cell
Nucleus
Endoplasmic
reticulum
Ribosomes
Mitochondrion
Lysosome
Golgi apparatus
Plant cells have a few plant-specific structures, including chloroplasts, a cellulose cell wall, and a central water vacuole.
Chloroplast
Cellulose cell wall
Water vacuole
Your Inner Bacterium
NUCLEAR ENVELOPE
The double membrane surrounding the nucleus of a eukaryotic cell.
MITOCHONDRIA
Membrane-bound organelles responsible for important energyconversion reactions in eukaryotes.
ENDOPLASMIC
RETICULUM
A membraneenclosed series of passages in eukaryotic cells in which proteins and lipids are synthesized. or “kernel”). It is surrounded by the nuclear
Antibiotics kill bacteria but leave humans un- envelope, a double membrane made of two harmed because their cells have different struc- lipid bilayers. The nucleus encloses the cell’s tures. Of all the ways that prokaryotic and DNA a nd ac ts as a k ind of cont rol center. Important reactions for eukaryotic cells differ, the most interpreting the genetic instrucobvious is the complexity of euAntibiotics kill tions contained in DNA take karyotic cells compared to their bacteria but leave place in the nucleus. smaller prokaryotic cousins. In
Other organelles in a eukaryparticular, eukaryotic cells— humans unharmed otic cell perform other specialboth animal and plant cells—are because their cells ized tasks. Mitochondria are characterized by the presence of have different the cell’s power plants—they multiple, distinct membranestructures. help extract energy from food bound organelles (Infographic and convert that energy into a
3.8).
You can think of a eukaryotic cell as a minia- useful form. Humans who inherit or develop ture factory with an efficient division of labor. defects in their mitochondria usually die—an
Each organelle is separated from the cell’s cyto- indication of just how important these organplasm by a membrane similar to the cell’s outer elles are (see Up Close: Eukaryotic Organelles).
Much like the plumbing system of a building, membrane, and each performs a distinct the endoplasmic reticulum (ER) is a vast netfunction.
The nucleus is the defining organelle of work of membrane-covered “pipes” that serve eukaryotic cells (from the Greek eu, meaning as a transport system throughout the cell. With
“good” or “true” and karyon, meaning “nut” the help of a protein “packaging plant” known
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UP-CLOSE
Eukaryotic Organelles
Nucleus
Endoplasmic Reticulum
The nucleus is the defining organelle of eukaryotic cells.
The nucleus is separated from the cytoplasm by a double membrane (two phospholipid bilayers), known as the nuclear envelope. The nuclear envelope controls the passage of molecules between the nucleus and cytoplasm. The nucleus contains the DNA, the stored genetic instructions of each cell.
In addition, important reactions for interpreting the genetic instructions occur in the nucleus.
The endoplasmic reticulum (ER) is an extensive, membranous intracellular “plumbing” system that is critical for the production of new proteins. The “rough ER” has a rough appearance because it is studded with ribosomes that are making proteins. The rough ER is contiguous with the “smooth ER,” the site of lipid production.
Rough endoplasmic reticulum
Smooth
endoplasmic reticulum DNA
(genetic material)
Nuclear envelope
Vesicle
Ribosomes
Golgi
The Golgi is a series of flattened membrane compartments, whose purpose is to process and package proteins produced in the rough endoplasmic reticulum. The processed molecules are packaged into membrane vesicles, then targeted and transported to their final destinations.
2. As the proteins make their way through the Golgi, they are processed.
3. Proteins are then packaged into transport vesicles, which deliver the proteins to their final destination.
1. Transport vesicle delivers proteins from the rough endoplasmic reticulum to the
Golgi.
Transport vesicle
The Nucleus, Endoplasmic Reticulum and Golgi Work Together to Produce and Transport Proteins
2. Proteins are made in the ER
Nucleus
and packaged into vesicles for transport to the Golgi.
3. Proteins receive final modifications in the Golgi. They are packaged into vesicles for transport to the site of protein function.
Cell membrane
1. The nucleus
Secreted from cell
provides instructions for protein production.
Endoplasmic reticulum
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Various locations within cell
Golgi
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UP-CLOSE
Eukaryotic Organelles
Mitochondria
Chloroplast
Mitochondria are found in almost all eukaryotes, including plants. Mitochondria have two membranes surrounding them.
The inner one is highly folded. Mitochondria carry out critical steps in the extraction of energy from food, and the conversion of that “trapped” energy to a useful form. They are the cell’s
“power plants.”
Chloroplasts are organelles found in algae and in the green parts of plants. Chloroplasts have two membranes surrounding them, as well as an internal system of stacked membrane discs.
Chloroplasts are the sites of photosynthesis, the reactions that plants use to capture the energy of sunlight in a usable form.
Ribosome
Ribosome
Granum
Thylakoid
membranes
Outer membrane
Inner membrane
Inner and outer membranes Lysosome
Lysosomes are the cell’s “recycling centers.” Full of digestive enzymes, lysosomes break down worn out cell parts or molecules so they can be used to build new cellular structures.
Outside of cell
Cytoplasm
Damaged cell parts are digested so their parts can be recycled.
Digestion
Cell membrane
The cell takes in molecules and brings them to a lysosome for digestion. The digested parts are then used in the cell for various functions.
Food and other particles
Lysosome
Golgi apparatus
Lysosome
Digestion
Cell membrane
Cytoskeleton
The cytoskeleton is a meshwork of protein fibers that carry out a variety of functions, including cell support, cell movement and movement of structures within cells. Each type of cytoskeletal fiber has a specific structure and function.
Microfilament
Intermediate filaments
Microtubule
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A supermarket pharmacy manager retrieves a bottle of antibiotics from the shelf. ganelles such as mitochondria as the Golgi apparatus, the ER and chloroplasts were once freetransports newly synthesized Overuse and misuse of living prokaryotic cells that beproteins to specific destinacome incorporated—engulfed—by tions, such as the cell mem- antibiotics have brane, other organelles, and led to an epidemic other free-living prokaryotic cells in a process dubbed even extracellular destinations of antibioticendosymbiosis. like the bloodstream.
Although many considered enOther eukaryotic organelles resistance. dosymbiosis a crazy idea at first, include the chloroplast, responsible for photosynthesis in plants, and ly- quite a bit of evidence now supports it. Mitochonsosomes, the cell’s recycling centers, which dria and chloroplasts are about the same size as digest and recycle molecules. In addition to bacteria, and to reproduce they divide in a manthese membrane-bound structures, a vast net- ner similar to prokaryotic cells. Both mitochonwork of protein fibers called the cytoskeleton dria and chloroplasts have circular strands of allows cells to move and maintain their shape, DNA, just like prokaryotic cells. They also contain ribosomes that are similar in structure to promuch the same way that your skeleton does.
Prokaryotic cells carry out similar functions karyotic ribosomes—so similar, in fact, that some of energy conversion and protein transport, but antibiotics that target prokaryotic ribosomes can they don’t contain these processes within sepa- affect the ribosomes in eukaryotic mitochondria, rate organelles; everything occurs in the which accounts for both the toxicity and the side cytoplasm. effects of these antibiotics.
How did eukaryotic cells develop their factory-like compartments? That question has Winning the Battle, Losing the War long intrigued biologists. One fascinating hy- To those who first benefited from its healing pothesis was proposed in the 1960s by biologist powers, penicillin seemed a wonder drug, a
Lynn Margulis, who argued that eukaryotic or- magic bullet. A once-lethal bacterial infection
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GOLGI APPARATUS
An organelle made up of stacked membraneenclosed discs that packages proteins and prepares them for transport. CHLOROPLAST
An organelle in plant and algal cells that is the site of photosynthesis. LYSOSOME
An organelle in eukaryotic cells filled with enzymes that can degrade worn-out cellular structures.
CYTOSKELETON
A network of protein fibers in eukaryotic cells that provides structure and facilitates cell movement. UNIT 1: WHAT IS LIFE MADE OF? CHEMISTRY, CELLS, ENERGY
1/27/11 10:14 AM
Drug-resistant strains of Neisseria gonorrhoeae are increasing in many countries.
ENDOSYMBIOSIS
The theory that freeliving prokaryotic cells engulfed other freeliving prokaryotic cells billions of years ago, forming eukaryotic organelles such as mitochondria and chloroplasts. could now be cleared in a matter of days with a course of antibiotic. Today, some of the most commonly prescribed drugs are antibiotics.
Antibiotics are so common, in fact, that many people routinely take them when they catch a cold or the flu. But antibiotics are powerless against these ills. That’s because viruses, not bacteria, cause colds and flu. Since viruses are not made of cells—and according to the cell theory are not even considered to be alive—they can’t be killed with an antibiotic.
But that doesn’t stop people from trying. In
2010, the American College of Physicians estimated that of the more than 133 million courses of antibiotics prescribed in the United States each year, as many as 50% are prescribed for colds and other viral infections. What’s more, many patients who are prescribed antibiotics for bacterial infections use them improperly.
Taking only part of a prescribed dose, for example, can spare some harmful bacteria living in the body, and those bacteria that survive are often heartier and more resistant to the antibiotic than the ones that were killed. Such overuse and misuse of antibiotics have led to an epi-
demic of such antibiotic-resistance, which the
Centers for Disease Control and Prevention calls
“one of the world’s most pressing public health problems.” Fleming himself warned against this very danger. In his own research, he found that whenever too little penicillin was used or when it was used for too little time, populations of bacteria emerged that were resistant to the antibiotic. In a 1945 interview in the New York Times,
Fleming warned that improper use of penicillin could lead to the survival and reproduction of virulent strains of bacteria that are resistant to the drug. He was right. In 1945, when penicillin was first introduced to the public, virtually all strains of Staphylococcus aureus were sensitive to it. Today, more than 90% of Staphyloccocus aureus strains are resistant to the antibiotic that once conquered this common microbe. (For more on antibiotic-resistant bacteria, see Chapter 14.)
Today, more than 90% of
Staphylococcus aureus strains are resistant to the antibiotic that once conquered this common microbe. Because of the alarming growth in antibioticresistant superbugs, drug companies and researchers are trying to develop new antibiotics.
One strategy they employ is to tweak the chemical structure of existing antibiotics just enough that a bacterium cannot disable it. Another approach is to look for antibiotics that target other bacterial weaknesses.
But all these efforts would be nothing without the man who gave a moldy petri dish a second glance nearly a century ago. That famous dish now sits in the museum at St. Mary’s Hospital in London. For his pioneering research,
Alexander Fleming—along with Oxford researchers Howard Florey and Ernst Chain—was awarded a Nobel prize in 1945. ■
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Summary
■■Antibiotics are chemicals,
■■Bacteria are surrounded by a
originally produced by living organisms, that selectively target and kill bacteria.
cell wall containing peptidoglycan, a molecule not found in eukaryotes. Some antibiotics, like penicillin, work by preventing peptidoglycan synthesis. ■■According to the cell theory, all
living organisms are made of cells. New cells are formed when an existing cell reproduces.
■■There are two types of cells,
distinguished by their structure: prokaryotic and eukaryotic.
■■Prokaryotic cells lack
membrane-bound organelles; eukaryotic cells have a variety of membrane-bound organelles.
■■All cells are enclosed by a cell
membrane made up of phospholipids and proteins. The cell membrane controls passage of molecules between the exterior and the cytoplasm of the cell.
■■Small hydrophobic molecules
can cross cell membranes by the process of simple diffusion.
■■Large or hydrophilic molecules
need to be transported across the membrane with the help of membrane proteins.
■■Facilitated diffusion is
transport down a concentration gradient; it does not require energy. Active transport is transport up a concentration gradient; it requires energy.
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■■All cells have ribosomes,
complexes of RNA and proteins that synthesize new proteins.
■■Despite their common
function, the structure of prokaryotic and eukaryotic ribosomes differs. Some antibiotics, like streptomycin, work by interfering with prokaryotic ribosomes.
■■Eukaryotic cells contain a
number of specialized organelles including a nucleus, endoplasmic reticulum, Golgi apparatus, mitochondria, chloroplasts, and other organelles, each of which carries out a distinct function. ■■Eukaryotic cells likely evolved
as a result of endosymbiosis, the engulfing of one single-cell prokaryote by another.
■■Increased and sometimes
inappropriate use of antibiotics has lead to the emergence of antibiotic-resistant bacteria.
Infections caused by these bacteria are very hard to treat.
UNIT 1: WHAT IS LIFE MADE OF? CHEMISTRY, CELLS, ENERGY
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Chapter 3 Test Your Knowledge
CELLULAR BASIS OF LIFE
Cells are the fundamental unit of life. All living things are made of cells, and all cells come from the division of pre-existing cells.
HINT See Infographics 3.2 and 3.4.
KNOW IT j 1. Describe the cell theory.
2. Which of the following statements best explains why bacteria are considered living organisms?
a. They can cause disease.
b. They are made up of biological macromolecules. c. They move around.
d. They are made of cells.
e. They contain organelles.
3. What are the two main types of cells found in organisms? USE j IT
4. Consider the distinction between living and nonliving things.
a. If all living things are made of cells, should a virus be considered alive? What about the infectious agent—a prion consisting of a single protein—responsible for mad cow disease?
b. Following from your answer to part a, are all disease-causing agents—pathogens— alive? 5. According to the cell theory, all living organisms are made of cells. More specifically what do all living organisms have in common? For example, do all living organisms carry genetic instructions? Do their cells all have a nucleus? What other features do they have in common?
MEMBRANES AND TRANSPORT
All cells are surrounded by a membrane that contains the cell’s contents and acts as a semipermeable barrier to substances on either side of it. Many substances move across the membrane with the help of proteins.
HINT See Infographics 3.3 and 3.7.
KNOW IT j 6. The two major components of cell membranes are a. phospholipids and DNA.
b. DNA and proteins.
c. peptidoglycan and phospholipids.
d. peptidoglycan and proteins.
e. phospholipids and proteins.
7. If a solute is moving through a phospholipid bilayer from an area of higher concentration to an area of lower concentration without the assistance of a protein, then the manner of transport must be
a. active transport.
b. facilitated diffusion.
c. simple diffusion.
d. any of the above, depending on the solute
e. Solutes cannot cross phospholipid bilayers.
8. Consider the movement of molecules across the cell membrane.
a. What do simple diffusion and facilitated diffusion have in common?
b. What do active transport and facilitated diffusion have in common?
USE j IT
9. Why does facilitated diffusion require membrane transport proteins while simple diffusion does not?
10. Sugars are large, hydrophilic molecules that are important energy sources for cells. How can they enter cells from an environment with a very high concentration of sugar?
a. by simple diffusion
b. by osmosis
c. by facilitated diffusion
d. by active transport
e. by using ribosomes
11. Many foods—for example, bacon and salt cod— are preserved with high concentrations of salt. How can high concentrations of salt inhibit the growth of bacteria? (Think about the high solute concentration of the salty food, relative to the solute concentration in the bacterial cells. Now think about what will happen to the water in the bacterial cells under these conditions. What do you think will happen to the cells as a result?)
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PROKARYOTIC VS. EUKARYOTIC
CELLS
Prokaryotic cells and eukaryotic cells have different structures. Antibiotics are effective because of these differences.
HINT See Infographics 3.4–3.6 and 3.8.
KNOW IT j 12. Penicillin interferes with the synthesis of
a. bacterial cell membranes.
b. peptidoglycan.
c. the nuclear envelope.
d. membrane proteins.
e. ribosomes.
13. Bacteria have _______ cells, defined by the
____________________________.
a. prokaryotic; presence of a cell wall
b. eukaryotic; presence of organelles
c. eukaryotic; absence of a cell wall
d. prokaryotic; absence of organelles
e. eukaryotic; absence of organelles
14. Which of the following is associated with eukaryotic cells but not with prokaryotic cells?
a. cell membrane
b. cell wall
c. DNA
d. ribosome
e. nucleus
15. Briefly describe the structure and function of each eukaryotic organelle listed:
a. mitochondrion
b. nucleus
c. endoplasmic reticulum
d. chloroplast
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USE j IT
16. If you treated a bacterial infection with two different antibiotics, one that stopped bacterial reproduction and one (penicillin, for example) that inhibited the production of new peptidoglycan, would this use of penicillin be effective? Explain your answer.
17. If bacterial cells were placed in a nutrientcontaining solution that had the same solute concentration as the cytoplasm, and which also contained penicillin, would the cells burst? Explain your answer.
18. Fungi are eukaryotic organisms. Why is it more challenging to develop treatments for fungal infections (for example, yeast infections, athlete’s foot, and certain nail infections) than for bacterial infections? 19. Some inherited syndromes, for example TaySachs disease and MERFF (myoclonic epilepsy with ragged red fibers), interfere with the function of specific organelles. MERFF disrupts mitochondrial function. From what you know about mitochondria, why do you think the muscles and the nervous system are the predominant tissues affected in
MERFF? (Think about the activity of these tissues compared to, say, skin.)
SCIENCE AND ETHICS
20. Many patients attempt to pressure their physician to prescribe antibiotics for colds. If you were a doctor, would you prescribe an antibiotic for a cold? How would you explain your decision to your patient? UNIT 1: WHAT IS LIFE MADE OF? CHEMISTRY, CELLS, ENERGY
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