Journal article
Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 908.7KB, Terms of use)
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- Publisher copy:
- 10.1039/d3sc06551k
Authors
- Publisher:
- Royal Society of Chemistry
- Journal:
- Chemical Science More from this journal
- Volume:
- 15
- Issue:
- 7
- Pages:
- 2509-2517
- Publication date:
- 2024-01-15
- Acceptance date:
- 2024-01-01
- DOI:
- EISSN:
-
2041-6539
- ISSN:
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2041-6520
- Pmid:
-
38362406
- Language:
-
English
- Keywords:
- Pubs id:
-
1607236
- Local pid:
-
pubs:1607236
- Deposit date:
-
2024-05-01
Terms of use
- Copyright holder:
- John et al.
- Copyright date:
- 2024
- Rights statement:
- © 2024 The Author(s). Published by the Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
- Licence:
- CC Attribution (CC BY) 3.0
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