title: Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia.
abstract: Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.
authors.affiliation: Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
authors.forename: Daniela R
authors.initials: DR
authors.lastname: Melo
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Roger F
authors.initials: RF
authors.lastname: Castilho
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D008764:Methylmalonic Acid / Q000378:metabolism* / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology
chemical_list: D008764:Methylmalonic Acid