The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin
Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two...
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MDPI AG
2017-01-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/9/1/26 |
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| author | Alessandra F. Perna Miriam Zacchia Francesco Trepiccione Diego Ingrosso |
| author_facet | Alessandra F. Perna Miriam Zacchia Francesco Trepiccione Diego Ingrosso |
| author_sort | Alessandra F. Perna |
| collection | DOAJ |
| description | Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin. |
| first_indexed | 2024-04-13T00:27:11Z |
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| id | doaj.art-cff53e6d0d094ec7902b42fe0a6ce491 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-13T00:27:11Z |
| publishDate | 2017-01-01 |
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| spelling | doaj.art-cff53e6d0d094ec7902b42fe0a6ce4912022-12-22T03:10:34ZengMDPI AGToxins2072-66512017-01-01912610.3390/toxins9010026toxins9010026The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic ToxinAlessandra F. Perna0Miriam Zacchia1Francesco Trepiccione2Diego Ingrosso3First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, via Pansini 5, Bldg 17, Naples 80131, ItalyFirst Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, via Pansini 5, Bldg 17, Naples 80131, ItalyFirst Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, via Pansini 5, Bldg 17, Naples 80131, ItalyDepartment of Biochemistry, Biophysics and General Pathology, University of Campania “Luigi Vanvitelli”, School of Medicine, via Luigi de Crecchio 7, Naples 80138, ItalyLanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin.http://www.mdpi.com/2072-6651/9/1/26lanthioninehomolanthioninehydrogen sulfidehomocysteinehemodialysisuremic toxins |
| spellingShingle | Alessandra F. Perna Miriam Zacchia Francesco Trepiccione Diego Ingrosso The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin Toxins lanthionine homolanthionine hydrogen sulfide homocysteine hemodialysis uremic toxins |
| title | The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin |
| title_full | The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin |
| title_fullStr | The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin |
| title_full_unstemmed | The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin |
| title_short | The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin |
| title_sort | sulfur metabolite lanthionine evidence for a role as a novel uremic toxin |
| topic | lanthionine homolanthionine hydrogen sulfide homocysteine hemodialysis uremic toxins |
| url | http://www.mdpi.com/2072-6651/9/1/26 |
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