40-Year-Old Puzzle Related Liver Enzyme Function Solved

by Kathy Jones on  November 14, 2010 at 1:03 PM Research News
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The answer to a 40-year-long puzzle about a mysterious process by which a critical enzyme metabolizes drugs and chemicals in food has been found by Penn State University researchers.

Michael Green and colleagues have been able to "freeze in time" the workings of this family of enzymes produced by the liver that break down common drugs such as Tylenol, caffeine, and opiates, as well as nutrients in many foods.

The find may help development of a wide range of more efficient and less-expensive drugs, household products, and other chemicals.

Enzymes in the family named P450 pass through a critical chemical phase-change called "Compound I," whereby an oxygen molecule is temporarily added.

"This phase change happens quickly, and P450 just as quickly changes back to its original state," Green explained.

Green and his colleagues grew one of the P450 enzymes in E.coli -bacteria found in the human gut. They then developed a method to cool the enzyme at just the right rate-one one-thousandth of a second -- to "freeze in time" the formation process of Compound I.

Green also explained that different populations of humans vary in which version of the gene they carry, and thus, which version of P450 they produce.

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