New knowledge about NAT2–enzyme can help improve drug dosages

2020-09-08

Researchers at Uppsala University have identified previously unknown activity in the enzyme NAT2 affecting the body's metabolism and clearance of drugs. The study, expected to contribute to tailor-made drug treatments, is published in Angewandte Chemie International Edition.

Daniel Globisch, researcher in Chemical biology for biomarkers

The human body contains many different enzymes that convert molecules that are not part of our metabolism, such as those we receive through food and drugs. Over time, these enzymes have evolved in order to modify specific forms of molecules, which is important for our ability to secrete toxic compounds and drugs.

In the current study focusing on the enzyme NAT2 (N-arylamine acetyltransferase 2), Daniel Globisch, researcher at the Faculty of Pharmacy and SciLifeLab Fellow, discovered that the importance of this enzyme is even more extensive for human metabolism than previously known.

“We identified that NAT2 acetylates a number of endogenous metabolites that contain aliphatic amines, which have not previously been described as substrates of this enzyme. Our results demonstrate that NAT2 has the potential to metabolize the nearly 10 percent of our most commonly prescribed drugs that contain aliphatic amines,” states Daniel Globisch.

N-arylamine acetyltransferase 2 showing previously unknown capacity

NAT2 is therefore likely to play a key role in the uptake, efficacy and clearance of commonly used drugs containing non-aromatic amines. Researchers at Uppsala University are now proposing, with reference to their results, a reclassification of NAT2's catalytic activity.

“Our findings have great potential to help tailoring the dosage of drugs to individual patient needs to achieve personalized medicine,” says Tobias Sjöblom, co-leader of the study

The study was conducted in collaboration between Daniel Globisch's research group and Tobias Sjöblom, professor of tumor genetics at Uppsala University. The article Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine N-Acetyltransferase NAT2 is published in the journal Angewandte Chemie International Edition.

More information

Also see  Research in Chemical Biology for biomarkers at Uppsala University

Contact

Daniel Globisch, Department of Medicinal Chemistry
Email  daniel.globisch@ilk.uu.se
Phone  018-471 4287

Text: Magnus Alsne, SciLifeLab, photo: Mikael Wallerstedt, Wikipedia

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Last modified: 2021-06-22