UC Santa Cruz Review Summer/Fall 1995

Zapping the cell's spark plug

Our days are full of inputs and outputs that we take for granted. In goes food; out comes water and waste. We inhale oxygen; we exhale carbon dioxide. We put gas in our cars and drive away, belching exhaust.

A few of us could explain how a car's engine burns gas and oxygen to hurtle us down the road. But fewer still could describe how the cells in our bodies, in much the same way, burn food and oxygen to keep us rolling through life.

Olof Einarsdottir is no expert on cars, but she knows what happens in her cells. Indeed, few in the world know more than she does about one topic: How do our cells use oxygen? The answers lie in the workings of a substance called "cytochrome oxidase."

"Cytochrome oxidase is the biological enzyme system that reacts with oxygen and makes energy," says William Woodruff of Los Alamos. "It's what we live on."

Cytochrome oxidase anchors a chain of enzymes in the mitochondrion, the power plant of the cell. The enzymes harness the energy locked up in food, such as sugars. Just as an engine doesn't explode all of a car's gas at once, a cell doesn't squander sugar's rich energy in one burst. Rather, the enzymes break down each molecule of sugar in a series of controlled steps. Those steps release a cascade of charged particles, electrons, in the cell. Cytochrome oxidase uses the electrons to convert oxygen into water with relentless precision--nearly 1,000 times every second.

At the same time, the oxidase pumps a set of oppositely charged particles, protons, from one part of the mitochondrion to another, as if charging up a battery. This electrical and chemical imbalance sparks other enzymes to make an unstable compound called ATP. ATP is the chemical stuff that cells use to perform work, such as flexing a muscle or copying a strand of DNA.

Our bodies make and consume pounds of ATP every day. Cytochrome oxidase triggers much of that output. The enzyme is so potent that a 55-gallon drum full of it, if fed a constant supply of oxygen, electrons, and protons, would churn out 25 megawatts of power--enough to run 25,000 homes.

Einarsdottir has zeroed in on the energetics of cytochrome oxidase for more than ten years. She made her first mark as a graduate student. Scientists knew the oxidase held two atoms each of iron and copper, forming "metal centers" where most of the action occurs. Einarsdottir discovered that it also harbors a third copper atom, plus atoms of magnesium and zinc.

At UCSC, Einarsdottir has pioneered new ways of watching the rapid-fire reactions in the metal centers. When workers in her lab zap the oxidase with a laser, they can discern chemical changes that start as quickly as 40 billionths of a second--faster than any other group. Further, her team then probes the oxidase at snapshots in time, from billionths to hundredths of a second. This original method illuminates the reactions as they rifle from one step to the next.

As the reactions occur, the oxidase may create radical forms of oxygen and water. "If these radicals left the enzyme, they would damage the cell," Einarsdottir says. "But the enzyme makes them all the time, and we're fine. The metal centers must prevent the radicals from escaping. We're trying to find out exactly how that works."

Einarsdottir's group is also exploring one of the oxidase's most vexing riddles: How does it manage to transfer electrons and pump protons at the same time? Solving the riddle would be a major advance.

"This is exciting to biochemists, but it's basic knowledge," Einarsdottir says. Even so, she ventures to muse on the long-term potential: "Some day, we might be able to make an artificial system as efficient as the mitochondrion, where we could harness huge amounts of energy for power. But we'll only be able to do that if we know exactly how it functions in the cell."

--Robert Irion