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Your NCERT book says, almost in passing, that "almost all enzymes are proteins". In the early 1920s that sentence would have started an argument. The most famous enzyme chemists of the day thought enzymes were not proteins at all. This post tells how James Sumner settled the question with a bean, a cold window ledge and a lot of stubbornness, and includes a worked example on the reaction his enzyme catalyses.
Who was James Sumner?
His Nobel Prize biography says he was born in Canton, Massachusetts, on 19 November 1887. At school he was bored by everything except physics and chemistry. At 17 he was accidentally shot while hunting and lost his left arm below the elbow. He had been left-handed, so he relearned everything with his right hand and threw himself into sports, from tennis to clay-pigeon shooting.
He studied chemistry at Harvard and then biochemistry under Otto Folin at Harvard Medical School. Folin advised him to take up law instead, because he thought a one-armed man could never succeed in chemistry. Sumner ignored him, finished his PhD in 1914 and became an assistant professor at Cornell. He died on 12 August 1955, according to his Nobel facts page.
Why was isolating an enzyme so hard?
In his Nobel lecture of 12 December 1946, Sumner listed the obstacles. Richard Willstätter's school held that enzymes were neither lipids, carbohydrates nor proteins, and existed in tiny amounts. Enzymes are also fragile: once separated from the natural protectors in the raw material, they can be destroyed by heavy metals, oxidation or the wrong pH.
Sumner decided in 1917 to try anyway. He had little time, little apparatus and little money, and he called the project a "long shot". People told him it was foolish, which, he said, made him all the more certain it was worth doing. The Nobel biography adds that when he went to Brussels on a fellowship in 1921, the enzyme expert he planned to work with thought his idea of isolating urease was ridiculous.
Why urease and jack beans?
Urease breaks urea down into ammonia and carbon dioxide. Sumner already used it to measure urea in blood and urine. In 1916 other researchers had found that the jack bean, Canavalia ensiformis, held about 16 times more urease than the soybean. Urease was also easy to measure accurately, and acting on such a simple substrate, it was likely to be one enzyme rather than a mixture.
He started by grinding beans in a coffee mill. Along the way he crystallised other bean proteins, which he named concanavalin A and B. Extracts in 30 per cent alcohol worked well, but only when cold. With no ice chest, he wrote, "we used to place cylinders of 30 per cent alcoholic extracts on our window ledges and pray for cold weather."
What happened in 1926?
He tried dilute acetone instead, made by diluting 316 ml of acetone to 1000 ml. After a night in a newly bought ice chest, the liquid looked clear. Under the microscope it was full of tiny crystals of a shape he had never seen. They dissolved in water, tested positive for protein and had very high urease activity. He telephoned his wife: "I have crystallized the first enzyme." The paper, The isolation and crystallization of the enzyme urease84560-4), appeared in the Journal of Biological Chemistry in August 1926.
How did he prove the crystals were the enzyme?
His lecture lists the evidence:
Crystallisation raised purity by 700 to 1400 times, far more than any other method.
As much as 40 per cent or more of the urease in the filtrate came out with the crystals.
Recrystallising made the urease purer still.
Poisoning the bean meal with mercuric chloride or formaldehyde killed the activity and also stopped the crystals forming.
Most biochemists ignored or disbelieved him, the Nobel biography says. Opinion changed after John Northrop crystallised pepsin in 1930 and then other enzymes, showing Sumner had found a general method. In 1946 Sumner received half of the Nobel Prize in Chemistry "for his discovery that enzymes can be crystallized"; Northrop and Wendell Stanley shared the other half.
Worked example: the urease reaction
Urease catalyses CO(NH₂)₂ + H₂O → 2NH₃ + CO₂.
Suppose 6.0 g of urea is fully hydrolysed (a sample amount). Molar mass of urea = 12 + 16 + 2 × (14 + 2) = 60 g/mol, so 6.0 g is 0.10 mol.
Ammonia: 2 × 0.10 = 0.20 mol, and 0.20 × 17 = 3.4 g.
Carbon dioxide: 0.10 mol, and 0.10 × 44 = 4.4 g.
Check the mass balance: water used is 0.10 mol, or 1.8 g. 6.0 + 1.8 = 7.8 g of reactants, and 3.4 + 4.4 = 7.8 g of products.
A quick percentage check from the story: 316 ml of acetone in 1000 ml of solution is 31.6 per cent acetone by volume, a little stronger than the 30 per cent alcohol he had used before.
Was Sumner completely right?
Mostly. He told the Nobel audience that "all enzymes are proteins but not all proteins are enzymes". Later work added details. In 1975 Dixon and colleagues showed that jack bean urease is a metalloenzyme that uses nickel. And the NCERT Class 11 chapter on biomolecules notes that some nucleic acids also behave like enzymes, which is why it says "almost all". If cofactors and ribozymes feel confusing, the Fermi Concept Library covers every concept in biology and chemistry, so you can check how they fit together. Our enzymes for NEET biology guide covers the full chapter.
What can a student take from Sumner?
Choose the problem you can win. He picked the richest source and the easiest enzyme to measure.
Treat discouragement as data, not a verdict. His teacher, a colleague in Brussels and much of the field doubted him.
Change one thing and look closely. Swapping alcohol for acetone, then checking a single drop under a microscope, made the breakthrough.
Next step: write the urease equation from memory and calculate the mass of ammonia from 3.0 g of urea.
