When biochemist Paul Boyer first proposed in the 1970s a mechanism for the creation of ATP in mitochondria, it was an idea of such stunning novelty that nobody believed him. His theory: Trillions of tiny rotary engines spin in our bodies to churn out a steady flow of ATP molecules.

The generation of ATP, the primary source of energy for nearly all activities of living organisms, was a central problem in biochemistry for decades. Scientists assumed that the process worked like nearly all other enzymatic reactions that transfer phosphate to an existing molecule, in this case a molecule of ADP.

This led scientists to believe that the phosphate ion is taken up by some other molecule. The product is then converted by a series of metabolic reactions to a form that transfers the activated phosphate to ADP. Biochemists were confident that ATP was formed through lots of steps, but they failed to find any of the intermediate chemical products in the cell. In short, they didn't have a clue about how most of the ATP in our bodies was made.

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Boyer suggested instead that the enzyme ATP-synthase, which converts ADP and phosphate to ATP, acted like a tiny rotating machine. Rather than a series of complex reactions, the rotary engine manufactures ATP in a single step. His arguments were based upon sophisticated experiments with isotopes and complex reasoning that left most of his colleagues in the dust, but which fit the data on the chemical energetics of the process.

It was an amazing creative leap on Boyer's part; one made before the complete structure of ATP-synthase was even known. The fact that it worked in theory, however, didn't make it any more believable to his colleagues. Thousands of enzymes have been studied with no hint of rotary motion in any case.

The rotational model was extremely controversial at the time and acceptance would be decades in the coming. More than 20 years after Boyer first proposed the mechanism, researchers in Japan captured an image of the spinning machine in action, proving that he was right all along. As confirmation of his work, and reward for his perseverance, Boyer shared the Nobel Prize in Chemistry in 1997.

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Here's how Boyer's little engine works: One end of the ATP-synthase is embedded in the mitochondrial membrane. A gradient of positively charged protons across the membrane provides electrical energy to spin the engine. This spinning essentially deforms and spring-loads three binding sites on the ATP-synthase complex. In turn, each of the three sites are converted from a site that binds ADP and phosphate to the complex, to one that allows ADP to grab the phosphate to form ATP, and finally to a site that pops off the ATP.

Because so much energy is stored in the bond between phosphate and ADP, biochemists had assumed that this was the reaction that required the most energy. Here again, Boyer provided a surprise. He showed that the spring loading created by the spinning engine shaft made ATP-creation happen spontaneously. Energy was needed, however, to bind ADP and phosphate to the complex and to release the newly formed ATP into the cell.

Boyer's contribution, along with those of Peter Mitchell and other contemporaries, finally put to rest the old-fashioned notion that cells were essentially little bags of chemicals that, in the right combination and concentration, can react with each other regardless of their surroundings. We know now that the internal structures of cells, especially membranes and biochemical enzymes, actively participate in complex and highly precise ways to help drive the chemical processes that allow us to think, move, and stay alive.

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