The chemistry of life

About 60 per cent of an adult’s weight is water, on average, a little more in a lean body and less in one with more fat. Water fills every cell and bathes the outside of each one. It is there because the chemistry of life happens in it. Two molecules can react only if they meet, and dissolved molecules drift about and collide. Water dissolves more kinds of substance than almost any other liquid, which makes it the body’s solvent.

Its dissolving power comes from its shape. In a water molecule, an oxygen atom shares electrons with two hydrogen atoms but pulls them closer to itself. That leaves the oxygen end slightly negative and the hydrogen ends slightly positive, so the molecule is polar. Those charged ends grip salts and sugars and pull them into the water. Oil has no charged ends to grip, so it stays apart.

Shortly before the year 1000, the young scholars al-Bīrūnī and Ibn Sīnā exchanged letters of questions about nature. Two of al-Bīrūnī’s were about freezing: why does ice float on water, and why does a vessel break when its water freezes? Most substances shrink as they turn solid, so the solid sinks in its own liquid. Water does the opposite. It expands by about 9 per cent as it freezes, which cracks a full jar.

The cause is a pull between molecules. The slightly positive hydrogen of one water molecule is drawn to the slightly negative oxygen of the next. This attraction is a hydrogen bond, far weaker than the bonds inside a molecule. In ice these bonds hold each molecule to four neighbours in an open framework that takes more room. So ice is less dense than liquid water: it floats, and a pond freezes from the top.

The big molecules of life are chains. A starch molecule is anything from hundreds to hundreds of thousands of glucose units, joined together. A protein is a chain of amino acids, and DNA a chain of units called nucleotides. A large molecule built from many repeated small units is a polymer.

The joining follows one pattern. As two units link, one gives up a hydrogen atom and the other an oxygen-hydrogen pair, and these leave together as a molecule of water. Chemists call this a condensation reaction. Taking a polymer apart runs it backwards. A molecule of water is added across each link and the link breaks, which is called hydrolysis, from the Greek for loosening with water. Digestion is hydrolysis. It splits the starch in bread back into glucose and the protein in an egg into amino acids, small enough to be absorbed.

Sugars and starch are built from just three elements, carbon, hydrogen and oxygen, with twice as many hydrogen atoms as oxygen atoms, the same ratio as in water. Chemists of the 1800s read such formulas as carbon joined to water and named the family the carbohydrates. The name has stuck, although no water is hiding inside.

The central carbohydrate is glucose, with six carbon atoms, twelve hydrogen and six oxygen. It is the fuel the blood carries to every cell, and the unit that most larger carbohydrates are built from. Plants make it. In photosynthesis a leaf takes in carbon dioxide from the air and water from the soil and, with the energy of sunlight, joins them into glucose, giving off oxygen. Almost every carbon atom in your body was first pulled out of carbon dioxide in this way.

A cell cannot keep spare glucose loose, because so much dissolved sugar would draw water in and swell it. So living things store glucose as chains. Plants fill seeds and tubers such as wheat grains and potatoes with starch. Animals keep theirs as glycogen, mostly in the liver and the muscles. Plants also build their cell walls from a third chain of glucose, cellulose, the stuff of wood and cotton.

All three are made of the same glucose. What differs is how the units are linked. In starch and glycogen the links have one shape, which our digestive enzymes fit, so the starch in bread is cut back into glucose within hours. In cellulose every second glucose unit is turned over, giving each link a different shape that no human digestive enzyme fits. Cellulose passes through the gut uncut, as the fibre in food.

A fat molecule has a small backbone of glycerol with three long fatty acid chains attached, which is why chemists call it a triglyceride. The chains are almost nothing but carbon and hydrogen. With no charged ends for water to grip, fat will not dissolve in water and gathers into drops instead.

Fat is also the richest fuel in food. A gram of fat yields about 37 kilojoules, more than twice the 17 from a gram of carbohydrate or protein. The difference is oxygen. The carbon atoms of a sugar already carry a good deal of it, so they are partly burned before they start. A fatty acid contains much less oxygen, so each of its carbons has further to go before it becomes carbon dioxide, and gives out more energy on the way. That is why the body keeps its long-term reserve of fuel as fat.

Swap one of a fat’s three fatty acids for a group containing phosphate, and the molecule changes character. The new head carries an electric charge and is drawn to water, while the two remaining tails still avoid it. Such a molecule is a phospholipid.

Put phospholipids into water and they arrange themselves without help. The tails crowd together out of the water’s way and the heads turn outward to face it, so the molecules settle into a sheet two layers thick, tails inside and heads on both faces. That double layer is the basic skin of every cell, the membrane that holds its contents in. Small uncharged molecules such as oxygen slip straight through its oily middle. Charged ones, such as sodium ions, cannot cross unless a protein in the membrane lets them through.

Proteins do most of the body’s work. The enzymes that run its reactions, the haemoglobin that carries oxygen, the keratin of hair and the antibodies that fight infection are all proteins. Every one is a chain built from the same small set of units, the amino acids, of which twenty kinds are used. Each has a group containing nitrogen at one end and an acid group at the other, and the acid end of one links to the nitrogen end of the next, giving off water.

What makes one protein different from another is the order of its amino acids. With twenty kinds to choose from at each place, there are 400 possible chains just two units long and 8,000 three units long. A typical protein is hundreds of units long, so the possible orders are beyond counting, and a single cell makes thousands of different proteins.

A chain of amino acids is not yet a working protein. It folds. Attractions between the units along the chain, hydrogen bonds among them, pull it into one precise three-dimensional shape, and the shape is what does the job. Haemoglobin folds into pockets that each hold oxygen. An antibody’s tips take a shape that fits one kind of germ. The order of the units decides the fold. In 1961 Christian Anfinsen unfolded an enzyme with chemicals, then washed them away, and it folded back into its working shape by itself.

Heat or strong acid shakes the folds loose. The chain stays whole, but its shape is lost, and with it the protein’s work. The protein is denatured, and the change is usually permanent. The clear white of an egg turns solid and white in a hot pan because its proteins denature, and cooling never makes it clear again.

Most reactions in a body would barely move at 37 °C. Before two molecules can react, they must be pushed over an energy barrier, the activation energy, and at body temperature few of them have enough energy to get over it. Enzymes lower the barrier. An enzyme is a protein that works as a catalyst: it speeds up one reaction without being used up, so a single enzyme molecule can do the same job again and again.

The gains can be enormous. Left alone at room temperature, one step a cell needs in making the building blocks of DNA and RNA would take about 78 million years to happen to half of the molecules. Held in the grip of its enzyme, each molecule makes the same change in about 18 thousandths of a second.

Each enzyme acts on one kind of molecule, or a few close relatives, and ignores the rest. The reason is shape. Folded into its working shape, an enzyme has a pocket on its surface, its active site, shaped to fit the molecules it works on. A molecule that fits slots in, is changed and is released. One of the wrong shape cannot fit, and nothing happens to it. In 1894 the chemist Emil Fischer compared the fit to a lock and its key, and this choosiness is called specificity.

So the enzyme that cuts starch, found in saliva and in the gut, has a pocket that fits the links between starch’s glucose units. Cellulose’s links are shaped differently, turned the other way, and do not fit the pocket. That is why a cotton shirt, almost pure cellulose, could never feed you.

All the chemical reactions going on in a body at once, building molecules up and breaking them down, together make up its metabolism. The best known of them releases the energy in glucose. In respiration, glucose reacts with oxygen to give carbon dioxide and water, the same products a sugar cube gives when it burns. A flame lets the energy out all at once, as heat and light. A cell takes glucose apart in a long series of small steps, each run by its own enzyme, and catches much of the energy in a carrier molecule called ATP, about 30 of them for each glucose.

When oxygen runs short, as in a sprinting muscle, a cell can take glucose only part of the way. It turns it into lactic acid and gets just 2 ATP. Once oxygen returns, the lactic acid is burned as fuel or rebuilt into glucose.

Some substances are needed in tiny amounts, yet the body fails without them. Many of them work alongside its proteins. The vitamins are small molecules of this kind that the body cannot make, or not enough of, and must get from food. Vitamin C is one. The enzyme that strengthens collagen, the tough protein of skin, gums, tendons and blood vessels, stalls without it. Go months without fresh fruit or vegetables and new collagen comes out weak, so gums bleed and old wounds reopen. That disease is scurvy.

Some minerals do similar work. Haemoglobin, the protein that carries oxygen in the blood, has an iron atom at the centre of each of its four haem groups, and each iron atom holds one oxygen molecule. About two-thirds of the body’s iron is in haemoglobin, so a diet short of iron leaves the blood short of haemoglobin.