Interference Implications

Kalamazoo College student at a conference in San Diego
Mara Livezey discussing the work with other scientists in San Diego.

The peer-reviewed publication Drug Metabolism Letters has accepted for publication the manuscript “Molecular Analysis and Modeling of Inactivation of Human CYP2D6 by Four Mechanism Based Inactivators.”

In addition to Associate Professor of Chemistry Laura Furge, the senior and corresponding author, the manuscript has six student co-authors: Mara Livezey ’13Leslie Nagy ’09Laura Diffenderfer ’11,Evan Arthur ’09David Hsi ’10, and Jeffery Holton ’13.

Their work described in this paper contributes to the understanding of how some drugs can halt the activity of an enzyme. In this case, the enzyme studied is one that is important for the body’s processing of about 20 percent of medicines, particularly treatments for arrhythmia and other heart diseases, depression, and other maladies. Such understanding is vital because many people’s health depends on daily regimens of multiple medicines. Sometimes one drug can interfere with the very enzymes responsible for the processing and clearance of other co-administered drugs. This and other unwanted side effects are the number one cause of hospitalization in America.

The paper’s contribution to the understanding of how certain classes of drugs cause this interference with key enzymes will hopefully lead to more effective prevention of the phenomenon in the future.

The K research was funded by grants from the National Institutes of Health and the Howard Hughes Medical Institute and by the Department of Chemistry Hutchcroft Fund. The latter was established by a gift from alumni Alan ’63 and Elaine (Goff) Hutchcroft ’63.

The final version of the study was presented at the San Diego meeting of the American Society for Biochemistry and Molecular Biology.