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Otto Warburg revealed the helper molecules of metabolism

In the 1930s Otto Warburg discovered the yellow enzymes and identified flavin and nicotinamide as the active parts of the enzymes that move hydrogen in living cells.

Otto Warburg
Otto Warburg · 1883–1970
Person
Otto Warburg
Lived
1883–1970
Field
Biochemistry
From
German

The story

After explaining how cells activate oxygen, Otto Warburg turned to the other half of the chemistry of respiration: how cells remove hydrogen from food molecules so that it can eventually combine with oxygen and release energy. From 1931 he directed the Kaiser Wilhelm Institute for Cell Physiology in Berlin-Dahlem, and the decade that followed brought a remarkable run of discoveries.

In 1932 Warburg and his colleague Walter Christian discovered a yellow protein from yeast that was needed for cell respiration, the first of the so-called yellow enzymes, and the same year his laboratory achieved the first crystallisation of a flavin, the yellow pigment at their core. In 1935 he identified nicotinamide as the active group of the hydrogen-transferring enzymes and studied how such coenzymes bind to their proteins. Optical methods he developed between 1935 and 1937, based on the ultraviolet absorption of the reduced form of nicotinamide, gave biochemists a simple way to follow these reactions. In 1938 his group isolated and crystallised flavin adenine dinucleotide, the coenzyme now known as FAD, which cells build from riboflavin, vitamin B2.

The laboratory also crystallised a series of fermentation enzymes, among them enolase in 1941 and enzymes from muscle and tumours in the early 1940s, and worked out key steps in the way sugar is broken down during fermentation.

Warburg's Nobel biography states that the flavins and nicotinamide, together with the iron oxygenase he had found earlier, gave a complete account of oxidation and reduction in the living world. In 1944 Albert Szent-Györgyi, himself a Nobel laureate, nominated Warburg for a second Nobel Prize for the work on nicotinamide, the fermentation enzymes and the flavin of the yellow enzymes. According to the Nobel Foundation he was considered a worthy candidate but was not chosen that year, despite a later story that he had been selected and then blocked by the Nazi regime.

These coenzymes, built from vitamins, turned out to be essential to energy production in virtually every living cell. Together, these findings helped complete the chemical picture of how cells carry out oxidation and reduction.

Why it matters

FAD and the nicotinamide coenzymes are central to every textbook account of metabolism, and Warburg's work helped explain why vitamins such as riboflavin are vital to health.

About Otto Warburg

Biochemist who uncovered how cells breathe and discovered that tumours burn sugar by fermentation, the “Warburg effect”; Nobel laureate in 1931 who kept working in Nazi Berlin as a “Mischling.”

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Otto Warburg
1883–1970 · Biochemistry
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Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.

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