title: Mechanistic basis of hypermethioninemia.
abstract: Hypermethioninemia is a condition defined as elevated plasma methionine levels and may be a consequence of different conditions that include non-genetic and genetic causes. In severe cases, hypermethioninemia may lead to development of neurological and hepatic impairments, but mechanisms are still not well elucidated. Therefore, this review aims to reunite the knowledge acquired about the methionine-induced brain and liver toxicity focusing on the results obtained by studies from patients, in vitro experiments, and in vivo animal models. In general, some studies have shown that methionine decreases Na+,K+-ATPase activity, induces oxidative stress, increases acetylcholinesterase activity, and leads to dendritic spine downregulation in brain. Concerning to liver, hypermethioninemia seems to provoke changes in cell morphology, lipid accumulation, oxidative stress, inflammation, and ATP depletion. It is possible to infer that oxidative damage is one of the most important mechanisms responsible for methionine toxicity, since different studies showed that this amino acid induces oxidative stress in brain and liver tissues. Besides, reactive oxygen species may mediate other alterations induced by methionine, such as the reduction in brain Na+,K+-ATPase activity, and liver inflammation.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Bruna M
authors.initials: BM
authors.lastname: Schweinberger
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. wyse@ufrgs.br.|Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil. wyse@ufrgs.br.
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D050938:Glycine N-Methyltransferase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009422:Nervous System Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D050938:Glycine N-Methyltransferase; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Brain; Hypermethioninemia; Liver; Methionine; Oxidative stress