title: The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin.
abstract: 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.
authors.affiliation: First 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, Italy. alessandra.perna@unina2.it.
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Perna
authors.affiliation: First 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, Italy. miriam.zacchia@unina2.it.
authors.forename: Miriam
authors.initials: M
authors.lastname: Zacchia
authors.affiliation: First 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, Italy. francesco.trepiccione@ana.au.dk.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trepiccione
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", School of Medicine, via Luigi de Crecchio 7, Naples 80138, Italy. diego.ingrosso@unina2.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Ingrosso
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000097:blood; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism*; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D006435:Renal Dialysis; D013440:Sulfides / Q000097:blood*; D014511:Uremia / Q000097:blood / Q000378:metabolism*
chemical_list: D013440:Sulfides; D006710:Homocysteine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C001520:lanthionine; D000409:Alanine; D006862:Hydrogen Sulfide
keywords: hemodialysis; homocysteine; homolanthionine; hydrogen sulfide; lanthionine; uremic toxins