Researchers from SciLifeLab and Uppsala University have discovered a previously unknown enzymatic activity against important human endogenous substrates and common drugs while studying the robust metabolic detoxification process responsible for the clearance of toxic compounds and drugs.

The study, focusing on the investigation of one of the major metabolizing enzymes, N-arylamine acetyltransferase 2 (NAT2), was published in Angewandte Chemie International Edition.

The human body has a large repertoire of enzymes that convert molecules that are not part of our metabolism such as drugs and food-derived substances. These enzymes have evolved to modify specific molecule classes and have been intensely studied because of their effects on the clearance of drugs. The present study made the surprising discovery that the NAT2 enzyme also acetylates important metabolites of the human metabolism.

“Among the most significantly upregulated metabolites, we identified the polyamine spermidine, which has been identified as a key metabolite in aging and longevity.” says Daniel Globisch (SciLifeLab/UU), who co-led the study.

The NAT2 enzyme is known to acetylate arylamine-containing substrates, but spermidine only contains aliphatic amines. Additional polyamine containing substrates were identified, which suggest an unknown regulatory function of NAT2. The regioselective acetylation of spermidine by NAT2 answers a long-standing question in polyamine metabolism as the enzymatic source of diacetylspermidine formation was unknown.

Additionally, several commonly used drugs containing aliphatic amines with several 100 millions of annual prescriptions were also shown to be converted by NAT2. About 10 percent of the prescribed drugs have an aliphatic amine and are potential substrates of NAT2. The results demonstrate that acetylation by NAT2 may play a greater role in the metabolism, efficacy, and clearance of common drugs than previously thought.

“Our findings have great potential to help tailoring the dosage of drugs to individual patient needs to achieve personalized medicine.” says Tobias Sjöblom (SciLifeLab/UU), who co-led the study.

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Ok!Read More
Privacy & Cookies Policy

Privacy Overview

This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience.
Necessary
Always Enabled

Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.

Non-necessary

Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.