This year's Nobel Prize in Chemistry will be awarded to three researchers for "pioneering work" on enzymes that play key roles in the way our cells synthesize and burn fuel. American Paul Boyer and Briton John Walker shared half of the $1 million prize for their discovery of how each day an enzyme manages to synthesize kilograms of cellular fuel, known as adenosine triphosphate (ATP). Danish biophysicist Jens Skou took the other half of the prize for his discovery of another enzyme that is the body's biggest ATP user.
ATP is created in cellular power plants known as mitochondria. A series of enzymes inside these fuel cells break down energy-rich compounds formed by the metabolism of food, liberating energy that's used to pump positively charged particles called protons across a membrane inside the mitochondria. Researchers surmised in the 1960s that the resulting difference in charge across the membrane somehow caused a catalyst called ATP synthase, which is bound into the membrane, to create ATP.
By the 1970s, researchers had discovered that ATP synthase consists of three connected sets of protein assemblies: a wheellike structure lodged in an internal mitochondrial membrane, a rod with one end fixed to the wheel's hub, and a large cylinder that wraps around the other end of the rod. Previous work had shown that ATP is created at a trio of sites on the cylinder, and that the rod played a key role in turning on the catalytic activity at these sites. But again, the exact mechanism was unclear.
Boyer, a biochemist at the University of California, Los Angeles, put the pieces of the puzzle together. He theorized that as protons passed through the mitochondria membrane back to the central region, they caused the wheel--and the attached rod--to spin, forcing the rod to rotate within the stationary cylinder. This rotation in turn slightly altered the structure of a trio of active sites within the enzyme, causing each in turn to catalyze the binding together of building blocks that make up ATP, synthesize a molecule of ATP, and release it.
"It was a startling new idea," says Joseph Robinson, a pharmacologist at the State University of New York, Syracuse. In 1994, Walker and his colleagues at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom, verified Boyer's theory by using x-rays to create an atomic-scale map of the catalytic portion of the enzyme.
Skou, at Aarhus University in Aarhus, Denmark, approached the fuel cycle from the other end. In 1957, he discovered the first enzyme that burns up ATP to transport ions across cell membranes. Skou's enzyme, known as sodium, potassium-ATPase, uses about one-third of all the ATP the body generates to pump sodium and potassium ions across cell membranes, an activity essential for nerve signal firing as well as a host of other cell functions. Hundreds of related enzymes have since been discovered.