Aldehyde-mediated Inhibition of Asparagine Biosynthesis Has Implications for Diabetes and Alcoholism

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Feb 16

PMID 38362406

Authors

Tobias John

Nadia Saffoon

John Walsby-Tickle

Svenja S Hester

Felix A Dingler

Christopher L Millington

James S O McCullagh

Ketan J Patel

Richard J Hopkinson

Christopher J Schofield

Affiliations

Soon will be listed here.

Abstract

Patients with alcoholism and type 2 diabetes manifest altered metabolism, including elevated aldehyde levels and unusually low asparagine levels. We show that asparagine synthetase B (ASNS), the only human asparagine-forming enzyme, is inhibited by disease-relevant reactive aldehydes, including formaldehyde and acetaldehyde. Cellular studies show non-cytotoxic amounts of reactive aldehydes induce a decrease in asparagine levels. Biochemical analyses reveal inhibition results from reaction of the aldehydes with the catalytically important N-terminal cysteine of ASNS. The combined cellular and biochemical results suggest a possible mechanism underlying the low asparagine levels in alcoholism and diabetes. The results will stimulate research on the biological consequences of the reactions of aldehydes with nucleophilic residues.

Citing Articles

Formaldehyde quantification using gas chromatography-mass spectrometry reveals high background environmental formaldehyde levels.

Chothia S, Emms V, Thomas L, Bulman N, Monks P, Cordell R Sci Rep. 2024; 14(1):20621.

PMID: 39232096 PMC: 11375156. DOI: 10.1038/s41598-024-71271-z.

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