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Field · Emerged 1828 – 1961

Biochemistry

What chemical reactions keep a cell alive, and how does it power them?

4 chapters3 min read6 turning points1 open problem

Branched from
Cell Theory
Branched into
Cell Biology + Molecular Biology + Pharmacology + Protein Crystallography + Synaptic Transmission
Figures
Friedrich Wöhler, Louis Pasteur, Eduard Buchner, Leonor Michaelis, Maud Menten, James Sumner, Hans Krebs, Peter Mitchell

In brief

Biochemistry studies the chemistry of life: the molecules cells are made of and the reactions by which they build, break down and extract energy. Those reactions are catalysed by enzymes, proteins that speed them up by factors of millions or more, and organised into pathways, chains of small steps each run by its own enzyme.

In the nineteenth century many believed that living things contained a special vital force beyond chemistry. Biochemistry replaced that with ordinary chemistry done extraordinarily well. Fermentation without cells in 1897, enzymes identified as proteins in 1926, the citric acid cycle in 1937 and the chemiosmotic theory of energy in 1961 built a picture of metabolism that is the same, in its core, in bacteria and in people.

Key ideas

EnzymeEnters 1926

A protein that speeds up a specific chemical reaction without being used up. Almost every reaction in a cell has its own enzyme.

Metabolic pathwayEnters 1937

A sequence of reactions, each catalysed by an enzyme, that turns one molecule into another in small steps. The citric acid cycle is the central one.

Enzyme kineticsEnters 1913

How fast an enzyme works as its substrate becomes more plentiful. The rate rises and then levels off when the enzyme is saturated, as Michaelis and Menten described.

ATPEnters 1961 – 1978

Adenosine triphosphate, the cell's energy currency. Energy from food is used to make it, and breaking it down powers muscle, transport and synthesis.

ChemiosmosisEnters 1961 – 1978

Cells store energy by pumping protons across a membrane, and use the flow back through a molecular turbine, ATP synthase, to make ATP.

Draws on other domains

Chapter I

Chemistry or Life?

In the early nineteenth century many chemists believed that the substances of living things could only be made by a vital force. In 1828 Friedrich Wöhler made urea, a substance from urine, by heating an ordinary salt. He wrote to his mentor Berzelius that he could make urea without needing a kidney. It did not end vitalism at once. But over the century chemists made more and more natural compounds in the laboratory, and the special status of living chemistry faded.

Fermentation was the test case. Pasteur showed that it needs living yeast. Justus von Liebig insisted it was ordinary chemistry. In 1897 Eduard Buchner settled it by grinding yeast with sand and filtering out every cell. The juice still turned sugar into alcohol. The work was done by substances in the cell, enzymes, and both men had been partly right.

Chapter II

Enzymes

What were enzymes? In 1913 Leonor Michaelis and Maud Menten described how fast they work, treating each enzyme as binding its target before transforming it. In 1926 James Sumner crystallised the enzyme urease and showed it was a protein. The eminent chemist Richard Willstätter disputed it for years, but by the 1930s it was clear: enzymes are proteins, each shaped to catalyse one reaction.

Biochemists then traced how cells break down food. Sugar is split step by step, and in 1937 Hans Krebs, who had fled Nazi Germany, found the cycle of reactions in which the fragments are burned to carbon dioxide. Fritz Lipmann identified ATP as the molecule in which the energy is captured and spent. Every living thing, from bacteria to people, turned out to use the same core pathways.

Chapter III

A Closer Look: Your Weight in ATP

A resting adult uses around 2,000 kilocalories a day, about 8.4 million joules. Most of that energy passes through ATP. Food is oxidised, the energy is captured by making ATP, and ATP is broken down to power everything from muscle contraction to pumping ions across nerve membranes.

How much ATP is that? Under cell conditions, breaking one mole of ATP releases about 50 kilojoules. Only part of the energy in food ends up in ATP, perhaps 40–60%, the rest being lost as body heat. Taking about half:

0.5×8.4×106 J5×104 J/mol≈84 mol of ATP per day.\frac{0.5 \times 8.4 \times 10^6 \text{ J}}{5 \times 10^4 \text{ J/mol}} \approx 84 \text{ mol of ATP per day} .

A mole of ATP weighs about 507 grams, so that is roughly 40 kilograms of ATP made and broken down every day, and more during exercise. Estimates of this kind put daily ATP turnover at around a person's own body weight.

Yet the body contains only about 250 grams of ATP at any moment. So each ATP molecule must be rebuilt from its breakdown products, about 40,000/250=16040{,}000 / 250 = 160 times a day, roughly every nine minutes. The machine that rebuilds it is ATP synthase, a rotary motor in the mitochondrial membrane. Protons flowing through it turn a rotor about a hundred times a second, and each full turn makes three ATP molecules. That protons drive it is what Peter Mitchell proposed in 1961. The rotary motor itself was worked out later, by Paul Boyer and John Walker.

Chapter IV

Energy From a Membrane

Mitchell's chemiosmotic theory was the last great surprise of classical biochemistry. For years biochemists had searched for a chemical intermediate that links burning food to making ATP. Mitchell, working from a private laboratory in a restored Cornish manor house, argued that there was none. Respiration pumps protons across a membrane, and their flow back drives ATP synthesis. It was ridiculed for a decade and then confirmed. Bacteria, mitochondria and chloroplasts all make ATP this way, a sign of their shared ancestry.

By the 1950s biochemistry had also merged with genetics. The one gene–one enzyme idea tied genes to proteins, and molecular biology found how genes encode them. The structures of cell parts and how enzymes are organised in space became cell biology.

Applications

Where it is used

Open problems

Where the map runs out

Open

Can enzymes be designed as well as evolution makes them?

Open as of 2026; one fully computational design now rivals natural enzymes on a model reaction, but most are still far slower.

Natural enzymes speed reactions by enormous factors, sometimes by 101710^{17} or more. Since the 2000s, computer-designed proteins have been made that catalyse reactions no natural enzyme performs. But they are usually thousands of times less efficient until improved by rounds of laboratory evolution. In 2025 a fully computational design matched natural enzymes on one model reaction, the Kemp elimination, but that is not yet routine.

Why it is hard

An enzyme's power depends on precise positioning of atoms to fractions of an ångström, and on motions of the whole protein that computer models capture poorly. Knowing how a protein folds is not the same as knowing how it catalyses.

What resolving it unlocks

Enzymes made to order for green chemistry, drug manufacture and breaking down plastics, and a test of whether we understand catalysis at all.

› Sources (2)

Further reading

  1. Lane, N. (2005). Power, Sex, Suicide: Mitochondria and the Meaning of Life. Oxford University Press.

    A popular book on mitochondria and chemiosmosis.

  2. Fruton, J. S. (1999). Proteins, Enzymes, Genes: The Interplay of Chemistry and Biology. Yale University Press.

    A scholarly history of biochemistry.

  3. Berg, J. M., Tymoczko, J. L., Gatto, G. J. & Stryer, L. (2019). Biochemistry (9th ed.). W. H. Freeman.

    The standard textbook.