The Machine Tools of Life

Living cells are complex chemical factories, and whatever they manufacture, they use protein molecules called enzymes as their machine tools. Scientists probing the secrets of life have learned that enzymes are long chains of amino acids linked together in definite order and tightly coiled or folded. But no one is sure just how they work. Last week Biochemist Klaus Hofmann of the University of Pittsburgh offered a glimmer of understanding by announcing the first partial synthesis of a working enzyme.

For his model Dr. Hofmann selected ribonuclease, a much-studied natural enzyme that breaks down the ribonucleic acid found in all cells. With delicate skill, he split the ribonuclease into two parts, one containing 20 amino acids, the other containing 104. In this disjointed condition the enzyme has no effectiveness. It is like a machine tool with the motor separated from the cutting edge.

Dr. Hofmann patiently built a copy of the smaller fragment. After he had stuck 13 of the acids together, he joined his synthetic segment to the 104-acid remainder of natural ribonuclease. The reconstituted enzyme proved to have 70% of the activity of the natural substance. Apparently the seven amino acids, Nos. 14 to 20, that had been left out are like the chip collector on a lathe--useful but not essential.

Dr. Hofmann then synthesized an eleven-acid segment and joined it with the rest of the enzyme. This substance proved wholly inert. Apparently amino acids Nos. 12 and 13 that he had just eliminated are at the "active site" of the enzyme, like the cutting tool of a lathe.

There is nothing special about either of these two acids; they are common in most living organisms. So Dr. Hofmann and a host of colleagues are now trying to discover why they give the coils and folds of the ribonuclease chain the qualities of an enzyme. A solution to that problem will be a solution to one of the most intriguing mysteries in the study of life.

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