{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:37:25Z","timestamp":1792517845144,"version":"4.5.0"},"reference-count":239,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNAM-PAPIIT","award":["IN109026"],"award-info":[{"award-number":["IN109026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Sulfur-containing amino acids (SCAA) and their metabolites constitute an integrated metabolic network essential for central nervous system (CNS) function. In mammals, sulfur metabolism links one-carbon metabolism, the methionine cycle and the transsulfuration pathway, thereby connecting nutrient availability with redox regulation, methylation reactions, neurotransmitter synthesis and cellular adaptation to stress. Among these metabolites, methionine, cysteine, glutathione, taurine, homocysteine and hydrogen sulfide play key roles in neuronal physiology, mitochondrial homeostasis, synaptic plasticity and antioxidant defense. Alterations in SCAA metabolism have been increasingly associated with neurological and neurodevelopment disorders, which share common features such as oxidative stress, mitochondrial dysfunction, altered glutamatergic signaling, impaired methylation capacity and neuroinflammation. These pathological mechanisms are also observed following exposure to toxic metals, suggesting the existence of convergent pathways between environmental neurotoxicity and neurological diseases. Several studies showed that chronic exposure to arsenic, mercury, cadmium, lead, and other toxic metals disrupts sulfur amino acid homeostasis by affecting methionine remethylation, transsulfuration activity, glutathione synthesis and reactive sulfur species production. Due to sulfur-containing metabolites possessing antioxidant and metal-binding properties, these pathways are also involved in adaptive detoxification response. However, sustained disruption of sulfur metabolism may compromise neuronal resilience and increase vulnerability to neurological dysfunction. This narrative review integrates current evidence on the physiological roles of SCAA in the CNS, and examines how toxic metals disrupt sulfur metabolic pathways. By combining findings from experimental studies, human data and exploratory transcriptomic analyses, we propose that disruption of SCAA homeostasis represents a mechanistic link between environmental metal exposure and increased vulnerability to neurological disease.<\/jats:p>","DOI":"10.3390\/metabo16070461","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:41:38Z","timestamp":1782909698000},"page":"461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sulfur-Containing Amino Acid Homeostasis in the Central Nervous System: From Physiology Regulation to Metal-Induced Neurotoxicity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5737-858X","authenticated-orcid":false,"given":"Wendy Leslie","family":"Gonz\u00e1lez-Alfonso","sequence":"first","affiliation":[{"name":"Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Ignacio","family":"V\u00e1zquez-Cervantes","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itamar","family":"Flores","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Gonsebatt","sequence":"additional","affiliation":[{"name":"Sistema Nacional de Investigadoras e Investigadores, Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n, Mexico City 03940, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-0142","authenticated-orcid":false,"given":"Gonzalo","family":"P\u00e9rez de la Cruz","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Faculty of Sciences, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9182","authenticated-orcid":false,"given":"Sa\u00fal","family":"G\u00f3mez Manzo","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleli","family":"Salazar","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-312X","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Pineda","sequence":"additional","affiliation":[{"name":"Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8754","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"P\u00e9rez de la Cruz","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1636S","DOI":"10.1093\/jn\/136.6.1636S","article-title":"The Sulfur-Containing Amino Acids: An Overview","volume":"136","author":"Brosnan","year":"2006","journal-title":"J. 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