Unit 16 · Biology: Cells and Energy

Drop a paper clip flat onto still water and it floats. Steel is far denser than water, so it should sink. It floats because the surface of water acts like a thin, stretchy skin. That skin exists because water molecules pull on each other. A water molecule is one oxygen atom bonded to two hydrogen atoms, bent like a boomerang. The oxygen end carries a small negative charge and the hydrogen ends carry a small positive charge. A molecule with charged ends like this is called polar.

Opposite charges attract, so the hydrogen of one water molecule is pulled toward the oxygen of the next. This weak pull is a hydrogen bond. Each bond is easy to break, but there are so many that together they make water cling to itself. Scientists call that clinging cohesion. Cohesion holds the paper clip up, pulls water up a paper towel, and lets a column of water climb from a tree’s roots to its leaves without breaking.

The same charges make water a powerful solvent, a liquid that dissolves other things. Salt, sugar, oxygen gas and thousands of the molecules a cell uses are polar or charged, so water molecules surround them and pull them apart. Roughly 60 percent of an adult human body is water. Almost every reaction in a cell happens with the ingredients dissolved in it. Oils are not polar, so water will not mix with them. That refusal, as you will see, is exactly what a cell membrane is built on.

Hydrogen bonds also make water slow to heat and slow to cool. A lake takes weeks to warm in spring, which is why Chicago’s lakefront stays cooler than the suburbs in June. Your body, mostly water, resists sudden temperature swings the same way. And when water freezes, hydrogen bonds lock the molecules into an open pattern that takes up more space, so ice floats. A pond freezes from the top down and the fish below stay in liquid water all winter.

Burn a marshmallow, a leaf, or a strip of bacon and each one turns black. The black is carbon. Every living thing is built mostly from carbon, and the reason is a simple counting fact. A carbon atom can form four bonds. It can link to four other atoms, or to other carbons in chains, branches and rings, and still have room to attach hydrogen, oxygen and nitrogen. No other common element builds such large, stable, varied molecules.

Cells assemble small carbon units into giant ones called macromolecules, the way a train is built from cars. Carbohydrates are chains of sugar units. Glucose, a single sugar ring, is the fuel most cells burn. Plants link thousands of glucose units into starch for storage and into cellulose for their tough walls. Your body stores glucose chains as glycogen in liver and muscle.

Lipids are the fats, oils and waxes. Most are long chains of carbon and hydrogen with almost no oxygen, so they are not polar and water will not dissolve them. That makes them good for storing energy in a compact form and for building membranes. A special lipid with one polar end and one oily end, the phospholipid, is the main material of every cell membrane you own.

The other two families, proteins and nucleic acids, do the cell’s work and hold its instructions. They get their own lesson. For now, notice the pattern: a few kinds of small units, joined in different orders and lengths, make an almost endless variety of large molecules. Every organism on Earth uses the same four families. That shared chemistry is one of the strongest pieces of evidence that all life is related.

Crack an egg into a hot pan and the clear liquid turns white and firm. Nothing was added. Heat changed the shape of the egg’s proteins, and shape is everything for a protein. A protein is a chain of small units called amino acids. There are 20 kinds of amino acids, and a typical protein links a few hundred of them in a specific order. The chain then folds into a precise three-dimensional shape, and that shape decides what the protein can do.

Proteins are the cell’s tools and machines. Some are structural, like the collagen in your skin and the keratin in your hair. Some carry things: hemoglobin in red blood cells carries oxygen. Some are gates in membranes. Some receive signals, and some, the enzymes, run chemical reactions. A single human cell contains thousands of different proteins, each with a job set by its folded shape. Heat, acid or the wrong salt level can unfold a protein, which is why a high fever is dangerous.

Where does a cell get the recipe for each protein? From its nucleic acids, the fourth family of macromolecules. DNA is a long double chain built from four kinds of units, called bases and lettered A, T, G and C. The order of those letters spells out the order of amino acids in every protein. A working copy of a gene is made in a related molecule, RNA, which carries the recipe out to the cell’s protein-building machines.

One cell of yours holds about 2 meters of DNA. It is coiled and packed into a nucleus far smaller than the dot on this i. Every cell in your body carries the same DNA. But a skin cell and a nerve cell read different pages of it. That is the idea to keep. Proteins do the work. DNA stores the instructions. The same set of instructions can be read in different ways.

Put a drop of hydrogen peroxide on a cut and it foams. Put the same drop on the counter and nothing happens for hours. Your blood and skin cells contain an enzyme called catalase. It grabs hydrogen peroxide molecules and splits them into water and oxygen gas thousands of times per second. The foam is the oxygen. Hydrogen peroxide would break down on its own eventually, but far too slowly to matter. The enzyme does not change what happens. It changes how fast.

Almost every reaction in a cell needs a push to get started, an energy hill called activation energy. An enzyme lowers that hill. It has a pocket, the active site, shaped to fit one particular molecule, its substrate. When the substrate settles into the active site, the enzyme bends it or holds it next to a partner, and the reaction happens with much less push. The product leaves, and the enzyme, unchanged, grabs the next substrate.

Because the fit is so exact, each enzyme usually handles one job. Amylase in your saliva breaks starch into sugars, which is why a cracker tastes sweet after you chew it for a while. Lactase breaks down milk sugar, and people who stop making it become lactose intolerant. Pepsin works only in the strong acid of the stomach. Move an enzyme out of its normal temperature or acidity and its shape shifts, the active site no longer fits, and the reaction slows or stops.

For a long time nobody knew what enzymes were made of. In 1926 the American chemist James Sumner ground up jack beans, purified the enzyme urease, and coaxed it into crystals. The crystals were pure protein. That settled the question, and Sumner later shared a Nobel Prize for it. Today enzymes are used to make cheese, soften jeans, brew beer, remove stains in cold water and copy DNA in every genetics lab on Earth.

In 1665 the English scientist Robert Hooke sliced a thin sliver of cork, put it under a microscope he had built, and saw rows of tiny empty boxes. They reminded him of the small rooms, or cells, that monks lived in, so he called them cells. The name stuck. What Hooke saw were the dead walls of plant cells, but it was the first time anyone had described the box-like units that living things are built from.

A decade later a Dutch cloth merchant, Antonie van Leeuwenhoek, ground lenses so fine that he could see single living creatures swimming in a drop of pond water. He called them animalcules, little animals. He found them in rain, in scrapings from his teeth, and in almost every liquid he looked at. Nobody had imagined a whole world too small to see. Many scientists did not believe him until they looked for themselves.

It took nearly two more centuries to turn these sightings into a rule. In 1838 the botanist Matthias Schleiden argued that all plants are made of cells. In 1839 Theodor Schwann showed the same for animals. In 1855 the physician Rudolf Virchow added the last piece: every cell comes from a cell that already existed. Cells do not form from slime or dust. They divide. Together these ideas are the cell theory: all living things are made of one or more cells, the cell is the basic unit of life, and all cells come from other cells.

Cell theory sounds obvious now, but it changed medicine. If cells come only from cells, then disease is something that happens to cells. A tumor is cells dividing when they should not. An infection is foreign cells multiplying inside you. Virchow’s line, all cells from cells, is still the foundation of pathology, the science of what goes wrong in the body.

Scrape the inside of your cheek onto a slide and stain it. Under the microscope you see wide, flat cells, each with a dark dot near the middle. Now look at a drop of yogurt. The living things there are hundreds of times smaller, plain rods and spheres with no dot at all. You have just seen the two great kinds of cells on Earth. The dot is a nucleus, a membrane-wrapped compartment holding the cell’s DNA. Cells with a nucleus are eukaryotic. Cells without one are prokaryotic.

Prokaryotes are bacteria and their less familiar cousins, the archaea. A typical bacterium is 1 to 5 micrometers long; a micrometer is one thousandth of a millimeter. Its DNA is a single loop floating in the cytoplasm. It has a tough cell wall, a membrane, ribosomes to build proteins, and often a whip-like flagellum to swim with. That is nearly the whole list. Prokaryotes are simple, but they are not primitive failures. They have lived on Earth for more than 3 billion years, and there are more bacterial cells in your gut than human cells in your whole body.

Eukaryotic cells are usually 10 to 100 micrometers across, ten times wider than a bacterium and often a thousand times the volume. Animals, plants, fungi and protists are all eukaryotes. Besides the nucleus, their cytoplasm holds organelles, small structures wrapped in their own membranes, each doing a specialized job. Remember the surface-to-volume problem from the chapter story. Organelles are part of the answer. Folding membranes inside the cell adds enormous surface area where reactions can happen.

Two organelles, mitochondria and chloroplasts, have their own small loops of DNA and their own ribosomes, and they look strikingly like bacteria. Most biologists accept the explanation that they once were bacteria. Long ago, an early eukaryotic cell swallowed them and, instead of digesting them, kept them. This idea, endosymbiosis, was argued most forcefully by Lynn Margulis in the 1960s and was doubted for years before the DNA evidence made it convincing.

Think of a eukaryotic cell as a small city. The nucleus is city hall, where the master plans, the DNA, are kept and copied. Orders leave the nucleus as RNA and go to the ribosomes, tiny factories that string amino acids into proteins. Some ribosomes float free. Many sit on a folded membrane maze called the endoplasmic reticulum, which finishes, folds and ships the proteins. A stack of flattened sacs, the Golgi apparatus, sorts and packages them for delivery inside or outside the cell.

Mitochondria are the power plants. They take in sugar and oxygen and release the energy in a form the cell can spend, a molecule called ATP. Cells that do a lot of work carry a lot of them. A heart muscle cell may be packed with thousands. Lysosomes are the recycling plants, small bags of enzymes that break down worn-out parts and swallowed bacteria. The cytoskeleton, a network of protein fibers, is the framework of roads and girders that holds the shape and moves things around.

Plant cells have three extras. A chloroplast is a green organelle that captures sunlight and builds sugar, the subject of the next chapter. A large central vacuole holds water and keeps the cell firm, which is why a well-watered plant stands up and a dry one droops. And outside the membrane sits a stiff cell wall of cellulose. Animal cells have none of these. Bacteria have a wall too, but of a different material, which is why some antibiotics can attack bacteria without harming your cells.

Look at a cell’s organelles and you can guess its job. A cell in your pancreas that makes digestive enzymes is crowded with endoplasmic reticulum and Golgi. A sperm cell is little more than a nucleus, a tail and a ring of mitochondria to power it. A leaf cell in the sun is stuffed with chloroplasts, while a root cell of the same plant has none. Same organism, same DNA, different equipment for different work.

Hooke’s microscope magnified a few dozen times. A classroom microscope today, like the one on this site, uses a 10x eyepiece and a set of objective lenses. Multiply the two numbers to get the total. A 4x objective gives 40x, enough to see a whole insect wing. The 40x objective gives 400x, where cheek cells fill the view and their nuclei show clearly. The 100x objective, used with a drop of oil between lens and slide, gives 1,000x, about the limit for a light microscope.

Magnifying more does not always show more. Every microscope has a resolution limit, the smallest gap between two points that it can still show as two points instead of one blur. For light microscopes that limit is about 0.2 micrometers, set by the wavelength of visible light itself. Blow the image up past that and it just gets bigger and fuzzier. To see the ribosomes, the membranes, or a virus, you need an electron microscope, which uses a beam of electrons with a much shorter wavelength and can resolve details thousands of times finer.

The other problem is that most cells are nearly transparent. Water in water is hard to see. So microscopists use stains, dyes that stick to particular parts. Methylene blue binds to DNA and turns the nucleus a deep blue. Iodine turns starch grains in a potato cell almost black. In 1884 the Danish doctor Hans Christian Gram found a stain that turns some bacteria purple and others pink, depending on the chemistry of their cell walls. Gram staining is still one of the first tests a hospital lab runs on a sample.

Staining usually kills the cell, so a stained slide is a snapshot, not a movie. Modern labs get around that by attaching glowing fluorescent tags to specific proteins in living cells and filming them. But the logic has not changed since Hooke. Magnify enough to see the structure, add contrast so it stands out, and be honest about what the instrument can and cannot resolve.

Shake oil and water in a jar and they separate again in seconds. That separation is the cell’s oldest trick. A phospholipid is a molecule with a polar head that loves water and two long oily tails that avoid it. Put millions of them in water and they arrange themselves so that every tail is hidden from water and every head touches it. The result is a double layer, the bilayer, with tails sandwiched in the middle. It forms on its own, and it heals its own tears.

That bilayer is the cell membrane. It is about 7 to 8 nanometers thick, so thin that a stack of ten thousand would be about the thickness of a sheet of paper. Because the middle of the sheet is oily, water-loving things like sugar, salt ions and proteins cannot pass through it on their own. Small nonpolar molecules such as oxygen and carbon dioxide slip through easily. That is what scientists mean when they call the membrane selectively permeable: some things get through, some do not.

The membrane is not a plain sheet. Proteins are embedded in it like boats in a harbor, and they can drift sideways, which is why the standard picture is called the fluid mosaic model. Some proteins are channels, tunnels lined with polar groups so that ions or water can pass. Some are carriers that grab a molecule on one side and release it on the other. Some are receptors that catch a signal outside and pass the message inside. Some are identity tags that tell your immune system this cell belongs to you.

Every cell has a membrane. Eukaryotic cells have many more inside, around the nucleus and each organelle. All of them use the same bilayer design. Understanding that one thin, oily, self-sealing sheet explains a lot. It explains why sugar you drink takes time to reach your blood. It explains why anesthetic gases, which are nonpolar, slip into nerve cells so easily. And it explains how a cell keeps an inside chemistry completely different from the outside.

Someone opens a bottle of perfume at the front of the room. Thirty seconds later the back row smells it. No fan moved the air. Molecules are always jiggling, and random jiggling spreads them out from where they are crowded to where they are scarce. This is diffusion. It happens on its own, with no energy spent by anyone, and it stops only when the molecules are evenly spread. The difference in crowding between two places is called a concentration gradient, and diffusion always runs down the gradient.

Diffusion is how oxygen gets into your blood and carbon dioxide gets out. Air in the lungs has more oxygen than blood does, so oxygen diffuses across the thin lung lining into the blood. Blood arriving at a muscle has more oxygen than the working muscle, so it diffuses out again. Ions and sugars, which cannot slip through the oily membrane, diffuse through channel and carrier proteins instead. That is called facilitated diffusion, but it still runs downhill and costs the cell nothing.

Water diffuses too, and water crossing a membrane gets its own name: osmosis. Water moves toward the side where dissolved particles are more concentrated, because that is where the water itself is less concentrated. Sprinkle salt on a slice of cucumber and it weeps. The salt outside draws water out of the cells. Drop a wilted lettuce leaf into plain water and it stiffens, because water flows into its cells until each vacuole presses hard against the cell wall. Plant cells depend on that pressure to stand up.

Animal cells have no wall, so osmosis can be dangerous. A red blood cell dropped into pure water swells until it bursts. Dropped into strong salt water, it shrivels. That is why hospitals give fluids in a solution with the same total concentration as blood, called isotonic, about 0.9 percent salt. It is also why drinking seawater makes you thirstier: the salt pulls water out of your cells and your kidneys need extra water to flush it out.

A nerve cell keeps far more potassium inside than outside, and far more sodium outside than inside. Diffusion is trying to erase both differences every second. The cell fights back with a protein pump. The sodium-potassium pump grabs three sodium ions from inside, uses one molecule of ATP, changes shape, and shoves them out. Then it takes two potassium ions from outside and brings them in. Moving molecules against their concentration gradient, using energy, is active transport.

Active transport is expensive. A resting nerve cell spends a large share of its ATP just running these pumps, which is part of why the brain, only about 2 percent of your body weight, burns roughly 20 percent of your energy at rest. But the gradients are worth it. The stored difference in charge across a nerve membrane is what lets a nerve fire. Kidney cells use active transport to pull salt back out of urine. Root cells use it to draw scarce minerals from soil into the plant.

Some cargo is far too big for any channel or pump. For that, the membrane itself moves. In endocytosis, the membrane folds inward around a particle, pinches off, and the particle floats inside the cell in a bubble of membrane called a vesicle. White blood cells eat bacteria this way, a form of endocytosis called phagocytosis. The reverse, exocytosis, lets a vesicle fuse with the membrane and dump its contents outside. That is how nerve cells release their signal chemicals and how pancreas cells release insulin.

Put the two lessons together and the membrane is a sorting system with several speeds. Small nonpolar molecules diffuse straight through. Ions and sugars diffuse through proteins, still for free. Things that need to go uphill get pumped, at a cost in ATP. Big packages are swallowed or spat out whole. The cell membrane is thinner than any material a person has ever manufactured, yet it does all of that at once.

Step out of a warm building onto a Chicago sidewalk in January with a wind off the lake. The air might be minus 20 degrees Celsius. Your core stays close to 37 degrees. Step into a July heat wave and your core is still close to 37. The outside swings by more than 50 degrees; the inside barely moves. Keeping the inside steady while the outside changes is homeostasis, and every living thing does it, from a bacterium to an oak.

The French physiologist Claude Bernard noticed this in the 1860s. He argued that complex animals live in two environments at once: the outer world and an inner sea of blood and tissue fluid that bathes every cell. Only because that inner sea stays constant can the animal move freely through a changing outer world. The American physiologist Walter Cannon later gave the idea its name, homeostasis, from Greek words meaning staying the same.

What gets held steady? Temperature. The amount of water. Blood sugar, which your cells need as fuel and which is dangerous both too high and too low. The acidity of the blood, kept within a very narrow range near a pH of 7.4. The levels of sodium, potassium and calcium. Oxygen and carbon dioxide. Each has a set point, a target value, and each has sensors and responses to nudge it back when it drifts. Homeostasis does not mean nothing changes. It means small changes trigger corrections.

A cell does the same thing on its own scale. It holds its internal salt and water in balance with the pumps and channels from the last section. It keeps its pH steady. When a cell’s homeostasis fails, the cell dies. When the body’s fails, we call it disease. Diabetes is blood sugar homeostasis breaking down. Heatstroke is temperature homeostasis overwhelmed. Much of medicine is the art of helping a body find its set points again.

A home thermostat is a machine for homeostasis. It has a sensor that reads the room temperature, a set point you choose, and a response, the furnace. Room gets cold, furnace turns on. Room warms past the set point, furnace turns off. The response undoes the change that triggered it. That is negative feedback, and negative here does not mean bad. It means the response pushes in the opposite direction from the change.

Your body runs on negative feedback loops. Sensors in your brain read blood temperature. Too warm, and blood vessels in your skin widen and sweat glands switch on; evaporating sweat carries heat away. Too cold, and skin vessels narrow to keep warm blood deep, and muscles shiver to make heat. After a sugary drink, blood glucose rises. The pancreas releases the hormone insulin, cells take up glucose, and the level falls. Hours later, when glucose dips, the pancreas releases a different hormone, glucagon, and the liver releases stored sugar. Two hormones, pushing opposite ways, hold glucose in a narrow band.

Positive feedback does the opposite. The response makes the change bigger. That sounds dangerous, and in a loop that never stops, it would be. But the body uses it for jobs that need to finish fast. When a blood vessel is cut, the first clotting proteins activate more clotting proteins, which activate still more, until a plug seals the wound. During childbirth, each contraction triggers release of a hormone that causes stronger contractions, until the baby is born and the loop ends. Positive feedback drives a process to completion, then stops.

When you meet a new body process, ask which kind of loop it is. Fever is negative feedback with a temporarily raised set point. Thirst is negative feedback for water. A panic that feeds on itself is positive feedback, and so is a runaway rumor. Engineers use the same two ideas in cruise control, in nuclear reactors and in the audio squeal when a microphone hears its own speaker. Cells invented feedback billions of years before we did.

Ask people where a tree’s weight comes from and most say the soil. It seems obvious. Roots are in the dirt, and the tree grows. Around 1640 a Flemish physician, Jan Baptist van Helmont, tested the idea. He weighed a young willow at 5 pounds and planted it in a tub with 200 pounds of dried soil. He added only water for five years, covering the tub so no dust could fall in. Then he weighed everything again. The willow had grown to 169 pounds. The soil had lost about 2 ounces.

The soil was not the answer. Van Helmont concluded the tree was made of water, which was closer than soil but still wrong. The real source was invisible to him: the air. A tree is mostly carbon, and that carbon enters as carbon dioxide gas through tiny pores in the leaves called stomata. Water from the roots supplies the hydrogen. A tree’s wood is, quite literally, air and water, rearranged and held together with energy from sunlight.

This is photosynthesis, from Greek words meaning putting together with light. In a green leaf, the pigment chlorophyll absorbs red and blue light and reflects green. That is why leaves look green to us. The absorbed light energy is used to pull carbon dioxide and water apart. The pieces are reassembled into sugar, mainly glucose, with oxygen gas as the leftover. The overall recipe fits on one line. Six carbon dioxides plus six waters, with light, make one glucose and six oxygens.

Every bite of food you have ever eaten traces back to this reaction. It came directly from a plant, or through an animal that ate one. The oxygen you are breathing came from it too. When you next see a cornfield outside Chicago, look at the stalks. By September there are tons of them per acre. They were built almost entirely out of the carbon dioxide in the air above the field.

A leaf cell may hold dozens of chloroplasts, each a green oval about the size of a bacterium. Inside each one, stacks of flat membrane discs sit in a thick fluid. The discs are the thylakoids, and their membranes are packed with chlorophyll. The fluid around them is the stroma. The two locations do two different jobs, and photosynthesis is really two linked processes that happen a few nanometers apart.

The first stage runs in the thylakoid membranes and needs light, so it is called the light-dependent stage. When a chlorophyll molecule absorbs a photon, an electron in it jumps to a higher energy level. That energized electron is passed along a chain of proteins in the membrane, and the energy it gives up is used to make two energy-carrying molecules, ATP and a related molecule called NADPH. To replace the lost electrons, the chloroplast splits water molecules. The hydrogen is kept; the oxygen is released as gas. The oxygen a plant gives off comes from water, not from carbon dioxide, a fact proved in 1941 by tracking a heavy form of oxygen through the reaction.

The second stage runs in the stroma and does not need light directly, only the ATP and NADPH from stage one. Here an enzyme grabs carbon dioxide from the air and attaches it to a five-carbon sugar. A cycle of reactions, worked out in the 1950s by Melvin Calvin using radioactive carbon as a tracer, rearranges the carbons and spends the ATP and NADPH to build a three-carbon sugar. Two of those make a glucose. The plant then links glucoses into starch to store, into cellulose to build, or ships them as sucrose to roots and fruits.

Notice what the plant has done. It turned light, which cannot be stored, into chemical bonds, which can. A potato in a cellar in February holds sunlight from August. The energy in glucose is real: burn a gram of sugar and it releases about 4 kilocalories, the same energy your cells will get from it, only more slowly and in smaller, usable steps.

A tomato plant on a windowsill in Rockford grows slowly in March and fast in June, even if it is watered the same. Sunlight is the difference. Photosynthesis, like any factory, runs at the pace of whatever it is shortest of. Biologists call the scarce ingredient the limiting factor. Add more of it and the rate climbs. Add more of something else and nothing changes. Finding the limiting factor is how greenhouse growers decide what to change.

Light is the first factor. In dim light, a plant makes sugar more slowly than it burns it and can starve in a bright room. As light increases, the rate rises, then levels off when something else runs short. Often that something is carbon dioxide, which is only about 0.04 percent of air. Commercial greenhouses sometimes pump extra carbon dioxide into the air around their tomatoes and cucumbers to lift the ceiling. Outdoors in a cornfield on a still July afternoon, the air right among the leaves can be measurably lower in carbon dioxide than the air above, because the plants are using it faster than the wind replaces it.

Temperature matters because the sugar-building stage is run by enzymes, and enzymes have a range they work in. Below about 10 degrees Celsius most crop plants slow to a crawl. Above roughly 40 degrees their enzymes begin to lose shape. Water matters in two ways. It is an ingredient, and it also controls the stomata. A thirsty plant closes its stomata to save water, which also shuts out carbon dioxide. On a hot, dry afternoon a plant may effectively stop photosynthesis to avoid drying out, even in full sun.

These limits explain a lot of the map of Illinois. Corn and soybeans are planted after the soil warms in spring. They grow fastest in the long, warm, wet days of June and July. A dry August cuts the harvest even if the sky is clear. Closed stomata mean no carbon coming in. Farmers, growers and crop scientists watch light, water and temperature closely. Whichever one is scarcest sets the size of the crop.

A gram of sugar holds about 4 kilocalories. If a cell released all of that at once it would cook itself. Instead, cells move energy in small, safe amounts using a molecule called ATP, adenosine triphosphate. Think of glucose as a hundred-dollar bill: valuable, but no vending machine takes it. ATP is the pocket change. A cell breaks the big bill into thousands of coins and spends them one at a time.

ATP is a small molecule with a tail of three phosphate groups. The bond holding the last phosphate on is under strain, because phosphates are negatively charged and repel one another. Snap that last phosphate off and energy is released, enough to power one step of work: one twitch of a muscle protein, one turn of a pump, one link added to a growing protein. What is left is ADP, adenosine diphosphate, with two phosphates. Add the phosphate back, using energy from food, and you have ATP again.

That recharge cycle runs constantly. A single ATP molecule in your body is used and rebuilt hundreds of times a day. Your cells hold only a few grams of ATP at any moment, yet over a full day they turn over roughly your own body mass in it. Nearly all that recharging happens in mitochondria, using the energy in glucose and oxygen. Stop the supply of oxygen, and the recharging stops within minutes. Brain cells, which cannot store much ATP, are the first to fail.

Every process from earlier chapters that needed energy needed ATP. Active transport pumps run on it. Ribosomes building proteins spend it. Cilia beat with it. Fireflies over a summer field in central Illinois make their light by using ATP to drive a reaction in a chemical called luciferin. The rest of this section asks the obvious question: how does a cell get the energy out of glucose and into ATP without setting itself on fire?

Run photosynthesis roughly backward and you get cellular respiration. One glucose plus six oxygens becomes six carbon dioxides plus six waters, and energy is released. It is the same overall change as burning sugar. But a cell does it in dozens of small enzyme-controlled steps. It catches the energy a little at a time in ATP. The carbon dioxide you breathe out is the carbon that was in your last meal, and before that in a plant.

The first stage, glycolysis, happens in the cytoplasm and needs no oxygen. Enzymes split the six-carbon glucose into two three-carbon molecules called pyruvate. This yields only 2 ATP net, a small down payment. If oxygen is present, the pyruvate enters a mitochondrion. There, in a cycle of reactions worked out by Hans Krebs in 1937, the carbons are stripped off one by one as carbon dioxide, and their high-energy electrons are loaded onto carrier molecules.

The real payoff comes in the inner membrane of the mitochondrion, which is folded into deep creases to increase its surface area. Those electrons are passed down a chain of proteins, and at each step the energy released pumps hydrogen ions across the membrane, building up a gradient. The ions flow back through a turbine-like enzyme that spins and snaps phosphates onto ADP. At the end of the chain, oxygen accepts the spent electrons and joins with hydrogen to form water. That is why you need oxygen: it is the final electron catcher. Without it, the whole chain backs up and stops.

Count it up and one glucose yields roughly 30 ATP by the full aerobic route. That is about fifteen times what glycolysis alone provides. This is why a heart cell is crowded with mitochondria. It is why your breathing speeds up when you climb stairs. The idea that a hydrogen ion gradient drives ATP production was proposed by Peter Mitchell in 1961. It was doubted for years before experiments confirmed it. It turned out to be the same trick chloroplasts use in the thylakoid. That is one more sign that the two processes are deep relatives.

Bread rises. Muscles burn near the end of a sprint. Milk turns into yogurt. All three are the same emergency plan. When a cell cannot get enough oxygen, the electron chain in its mitochondria stalls, and the carrier molecules that glycolysis needs are stuck full of electrons. Glycolysis would stop too, and with it the last trickle of ATP. Fermentation is the workaround. The cell dumps the extra electrons onto pyruvate, freeing the carriers, so glycolysis can keep making its 2 ATP per glucose.

Yeast dumps the electrons by turning pyruvate into ethanol and carbon dioxide. This is alcoholic fermentation. Bakers want the carbon dioxide: the bubbles it makes in dough are what lift a loaf, and the ethanol bakes off in the oven. Brewers and winemakers want the ethanol. In 1857 Louis Pasteur showed that fermentation was the work of living yeast cells, not a simple chemical decay, and he found that yeast fermented most when kept away from air. Give it oxygen and it switches to respiration and grows instead.

Your muscle cells cannot make ethanol. They turn pyruvate into lactic acid instead. During hard exercise, your heart and lungs cannot deliver oxygen as fast as the muscles use ATP, so the cells switch partly to lactic acid fermentation. It is fast but wasteful, and lactic acid builds up until you slow down. Once you stop and gasp for a minute, oxygen catches up, the lactic acid is carried to the liver and rebuilt into glucose, and normal respiration resumes. That extra breathing after a race is you paying off the debt.

The same bacteria that sour milk into yogurt and cabbage into sauerkraut use lactic acid fermentation, and the acid they make is what keeps other microbes from spoiling the food. Fermentation is also a window into the past. Glycolysis and fermentation work with no oxygen, and Earth’s early atmosphere had almost none. The first cells, billions of years ago, likely lived this way. The oxygen-using stages came later, after photosynthesis had filled the air with oxygen to catch the electrons.

Put the two processes side by side. Photosynthesis takes in carbon dioxide and water, stores energy, and releases oxygen. Respiration takes in oxygen and sugar, releases energy, and gives back carbon dioxide and water. The outputs of each are the inputs of the other. A carbon atom in a corn kernel in Illinois was in the air over that field in July. Eaten by a hog, it becomes part of a cell, is burned for energy, and returns to the air as carbon dioxide, ready for a leaf to catch it again next summer.

Plants do both. A leaf runs respiration all the time, day and night, in its mitochondria, because it needs ATP just as you do. In daylight, photosynthesis usually runs faster than respiration, so the leaf takes in more carbon than it gives off, and the plant gains mass. At night it only respires, and Ingenhousz was right that a plant in the dark spoils the air a little. Over a year, a growing forest is a net absorber of carbon. A forest that is rotting or burning is a net source.

You can see the planet doing this. Since 1958 a station on Mauna Loa in Hawaii has measured carbon dioxide in clean mid-Pacific air. The record shows a sawtooth. Every spring and summer, as the vast forests and fields of the Northern Hemisphere leaf out and photosynthesize, the number drops by several parts per million. Every autumn and winter, as leaves fall and rot and photosynthesis slows, it rises again. The Northern Hemisphere has most of Earth’s land, so its growing season sets the rhythm. Earth inhales in May and exhales in October.

Under the sawtooth, the yearly average has climbed steadily, from about 317 parts per million in 1960 to over 400 today. That rise is not from respiration. It comes mostly from burning coal, oil and gas, which releases carbon that photosynthesis buried underground hundreds of millions of years ago, faster than today’s plants and oceans can take it back up. Fossil fuel is ancient sunlight. Burning it is respiration on a planetary scale, without the matching photosynthesis.

You replace the entire lining of your gut about every week, and you replace your skin’s outer layer about every month. Every second, your bone marrow releases millions of new red blood cells. All of that comes from cells dividing, and each division is the end of a repeating sequence called the cell cycle. A cell that divides on schedule keeps you alive. One that divides off schedule is the subject of a later lesson.

Most of the cycle is interphase, when the cell looks calm under a microscope but is working hard. In the first gap phase, G1, it grows, makes proteins and organelles, and decides whether conditions are right to continue. In the S phase, S for synthesis, it copies every one of its chromosomes so that there are two complete sets of DNA. In the second gap, G2, it grows more and checks the copies. Only then comes M phase, mitosis, when the two sets are pulled apart and the cell splits.

The cycle has checkpoints, moments when the cell pauses and takes stock. Is it big enough? Is there enough food? Is the DNA damaged? Was every chromosome copied exactly once? A protein called p53 is one of the inspectors; if it finds broken DNA it halts the cycle until repairs are made, or if the damage is too great, orders the cell to destroy itself. Checkpoints are why most damaged cells never become tumors. They are the quality control of the body.

Different cells run the cycle at different speeds. Human cells growing in a lab dish take about 24 hours to go around once. Cells lining the gut divide faster. Mature nerve and heart muscle cells mostly leave the cycle altogether and never divide again, which is why damage to the brain or heart heals so poorly. Liver cells sit quietly for years but can re-enter the cycle when the liver is injured, which is why a liver can regrow much of itself after surgery.

In the 1880s the German anatomist Walther Flemming stained salamander cells with dyes and saw threads inside the nucleus thicken, line up, and pull apart in the dividing cell. He named the process mitosis, from the Greek for thread. The threads were chromosomes, though he did not know they carried genes. Under the microscope today, with a stain and a 400x objective, a root tip of an onion shows every stage he drew.

Before mitosis begins, S phase has already copied each chromosome. The two copies, called sister chromatids, stay attached at one point. The first stage is prophase. The loose DNA coils tightly into short, visible chromosomes. The membrane around the nucleus breaks down. A scaffold of protein fibers, the spindle, forms between the two ends of the cell. In metaphase, spindle fibers attach to each chromosome. They line all of them up along the middle of the cell, like players at a center line.

In anaphase the sister chromatids are pulled apart, one copy toward each end of the cell. This is the moment that matters: each end now has a complete, identical set. In telophase the chromosomes uncoil, and a new nuclear membrane forms around each set. Finally, cytokinesis divides the cytoplasm. An animal cell pinches in at the middle until it splits. A plant cell, with its stiff wall, instead builds a new wall down the center. The result is two cells, each with the same 46 chromosomes as the original, for a human.

Mitosis is copying, not mixing. The daughter cells are genetically identical to the parent, which is exactly what you want when replacing skin, healing a cut or growing from a fertilized egg to an adult. This is Virchow’s rule in action. A different kind of division, meiosis, makes sperm and egg cells with half the chromosomes each; it shuffles genes, and it belongs to the study of heredity.

Every day, some of your cells suffer damage to their DNA, from sunlight, from chemicals, from ordinary copying mistakes. Nearly all of it is repaired or the damaged cell destroys itself at a checkpoint. But a few genes are the control system itself: genes that step on the gas of the cell cycle and genes that hit the brakes. If a cell collects mutations that jam the gas and cut the brakes, it divides when it should not, and its daughters do too. That is cancer. It is not one disease but hundreds, and each one begins as a cell breaking the rules of the cycle.

A clump of runaway cells is a tumor. If the cells stay in one place and keep their neighbors’ boundaries, the tumor is benign and can usually be removed. A malignant tumor is one whose cells invade nearby tissue and, worst of all, travel through the blood or lymph to start new tumors elsewhere, a process called metastasis. Cancer cells also ignore the signals that tell normal cells to stop, evade the immune system, and grow new blood vessels to feed themselves. They are the body’s own cells, following broken instructions.

What damages the control genes? Tobacco smoke is the largest preventable cause; its chemicals mutate DNA in the lungs, mouth and bladder. Ultraviolet light from the sun damages skin cell DNA. Some viruses insert their genes into ours; the human papillomavirus causes most cervical cancer, which is why there is now a vaccine against it. Some people inherit a faulty brake gene and start with one strike already. And time itself matters: the older a cell line, the more mutations it has had a chance to collect, which is why most cancers appear later in life.

Because cancer is division gone wrong, most treatments attack dividing cells. Radiation and many chemotherapy drugs damage DNA or break the spindle, which hits fast-dividing cancer cells hardest but also hits hair follicles and the gut lining, causing the familiar side effects. Newer drugs target the specific broken proteins in a patient’s tumor. Much of what we know came from a single line of cells, taken in 1951 from a Baltimore woman named Henrietta Lacks, which has divided in labs around the world ever since. Her story also forced hard questions about consent that medicine is still answering.

You began as one cell. Nine months later you were tens of trillions, of roughly 200 different kinds. The first cell divided by mitosis into two identical cells, then four, then eight. Somewhere along the way, cells that were identical began to differ. Some became muscle, some nerve, some blood, some bone. This narrowing of a cell’s options is called differentiation. Once a cell has become a heart muscle cell, it and its descendants stay heart muscle.

Differentiation does not change the DNA. A nerve cell and a skin cell in the same person carry the same instructions. What differs is which genes are switched on. Signals from neighboring cells, from position in the embryo and from chemical gradients tell each cell which chapters of the DNA to read. A cell reading the muscle chapters fills with contracting proteins. A cell reading the blood chapters fills with hemoglobin and, in the case of a red blood cell, eventually throws away its nucleus.

A stem cell is a cell that has not finished choosing. It can divide to make more stem cells or produce cells that go on to specialize. The cells of a very early embryo are pluripotent: they can become any cell type of the body. Adult stem cells are more limited. The ones in your bone marrow can make any kind of blood cell, but not nerve or muscle. That is what a bone marrow transplant is: giving a patient whose blood-making stem cells were destroyed by disease or by cancer treatment a new supply from a donor.

In 2006, the Japanese scientist Shinya Yamanaka made a surprising discovery. Adding just four genes could turn an ordinary adult skin cell back into a pluripotent stem cell. He shared a Nobel Prize for it in 2012. These induced pluripotent stem cells let researchers grow a patient’s own nerve or heart cells in a dish. There they can study a disease or test a drug. Growing whole replacement organs remains far harder than headlines suggest. But the basic finding stands. Specialization is a setting, not a permanent rewrite, and it can be reset.

Take a single stride during a run and count what has to happen. Muscle cells in your leg burn ATP. To recharge it they need oxygen and glucose, delivered by blood. The blood is pushed by the heart and loaded with oxygen in the lungs. Breathing speeds up because sensors in the brain notice rising carbon dioxide. The glucose came from a meal, broken down in the gut and stored in the liver. Sweat glands dump heat. Kidneys adjust water and salt. One stride, and most of your body is involved.

Biologists describe this as levels of organization. Cells of the same type working together form a tissue, such as muscle tissue or nerve tissue. Several tissues combined into a structure with a job form an organ: the heart is muscle tissue, nerve tissue, connective tissue and a lining, all working together. Organs that cooperate on a larger task form an organ system. The heart, blood vessels and blood make up the circulatory system. The human body has about a dozen such systems.

The key idea is that systems interact. The circulatory system carries what the respiratory system takes in and what the digestive system absorbs. The nervous system and the hormones of the endocrine system coordinate the rest, using the feedback loops from the last chapter. The skeletal and muscular systems move the whole thing around. The excretory system, mainly the kidneys, cleans the blood that every other system has been dumping waste into. Damage one system and the others feel it: a failing heart leaves the kidneys short of blood, and failing kidneys let waste build up that poisons the heart.

Step back and the whole unit fits together. Water and carbon build molecules. Molecules build cells. Cells run on ATP made from sugar that came, through a plant, from sunlight. Cells divide by mitosis, specialize, and organize into tissues, organs and systems that keep the inner environment steady. Priestley’s mint and Priestley’s mouse were the two halves of one loop. You are the mouse’s side of it, made of about 37 trillion cells, every one of them descended from a single cell by the process in this chapter.