Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism.
Chem Sci
; 15(7): 2509-2517, 2024 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-38362406
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.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article