Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism
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 form...
| Główni autorzy: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Język: | English |
| Wydane: |
Royal Society of Chemistry
2024
|
| _version_ | 1826313157742690304 |
|---|---|
| author | John, T Saffoon, N Walsby-Tickle, J Hester, SS Dingler, FA Millington, CL McCullagh, JSO Patel, KJ Hopkinson, RJ Schofield, CJ |
| author_facet | John, T Saffoon, N Walsby-Tickle, J Hester, SS Dingler, FA Millington, CL McCullagh, JSO Patel, KJ Hopkinson, RJ Schofield, CJ |
| author_sort | John, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:08:47Z |
| format | Journal article |
| id | oxford-uuid:4d17df1f-8820-4bbd-8ce4-6f06d13e15a9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:08:47Z |
| publishDate | 2024 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:4d17df1f-8820-4bbd-8ce4-6f06d13e15a92024-06-07T13:19:28ZAldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholismJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4d17df1f-8820-4bbd-8ce4-6f06d13e15a9EnglishSymplectic ElementsRoyal Society of Chemistry2024John, TSaffoon, NWalsby-Tickle, JHester, SSDingler, FAMillington, CLMcCullagh, JSOPatel, KJHopkinson, RJSchofield, CJPatients 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. |
| spellingShingle | John, T Saffoon, N Walsby-Tickle, J Hester, SS Dingler, FA Millington, CL McCullagh, JSO Patel, KJ Hopkinson, RJ Schofield, CJ Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| title | Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| title_full | Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| title_fullStr | Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| title_full_unstemmed | Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| title_short | Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| title_sort | aldehyde mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism |
| work_keys_str_mv | AT johnt aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT saffoonn aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT walsbyticklej aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT hesterss aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT dinglerfa aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT millingtoncl aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT mccullaghjso aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT patelkj aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT hopkinsonrj aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism AT schofieldcj aldehydemediatedinhibitionofasparaginebiosynthesishasimplicationsfordiabetesandalcoholism |