CHAPEL HILL -- Contrary to what some scientists have suggested, key intracellular particles known as ribosomes serve as mechanical matchmakers or readout devices rather than acting chemically to speed up reactions in the body the way enzymes do, University of North Carolina at Chapel Hill researchers and colleagues have discovered.
A report on the findings by Drs. Annette Sievers and Richard Wolfenden of the UNC School of Medicine appears in the new issue of the Proceedings of the National Academy of Sciences.
Besides Sievers and Wolfenden, report authors are doctoral student Malte Beringer and Dr. Marina V. Rodnina of the University of Witten/Herdecke in Witten, Germany.
"Enzymes, of which we have hundreds, participate chemically in the transformation of biological molecules by making and breaking bonds," said Wolfenden, Alumni Distinguished professor of biochemistry and biophysics. "A hallmark of that direct chemical involvement is that their catalytic effects are extremely temperature dependent. The question was whether the ribosome acts as an enzyme since there has been considerable interest in whether this particle does that."
Ribosomes are critical sites of protein synthesis, he said. Inside those particles, amino acids are laid down in proteins in the order specified by the genetic code.
In general, enzymes, which are biological catalysts, facilitate a chemical transformation by lowering the energy barrier, Sievers said.
"One can imagine this as two paths over a mountain," she said. "The path without the enzyme is much higher, and so it takes more energy to cross the mountain. The path on the enzyme is lower, and so it is easier to follow it."
Energy has two components, Sievers said. One is heat (enthalpy), the other one refers to the order of a system (entropy). It's possible for an enzyme to lower either of those energy components. Direct chemical involvement of an enzyme is characterized by lowering the enthalpy of the activation barrier and has often been observed.
"In our present work we tested the contribution of enthalpy and entropy to lowering the activation energy barrier," she said. "Malte did this by comparing the energy barrier of the reaction when the ribosome was present, and I did it when the ribosome was not present."
The reactions both with the ribosome present and without the ribosome have the same enthalpic activation barrier, the researchers found.
"The means by which the ribosome speeds up the chemical transformation is purely entropic in origin -- the ribosome acts as a mechanical readout device, rather than speeding up the reaction in the way that conventional enzymes do," Sievers said.
The experiments will help scientists narrow their view of how ribsomes function and understand them better, Wolfenden said.
"Annette and Malte's discovery has important implications for the design of inhibitors of protein synthesis and might ultimately furnish a new basis for drug design," he said. "Their work shows that the ribosome's effect is to introduce order into chaos."
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