title: Brain energy metabolism is compromised by the metabolites accumulating in homocystinuria.
abstract: Homocystinuria is an inborn error of metabolism caused by severe deficiency of cystathionine beta-synthase activity. It is biochemically characterized by tissue accumulation of homocysteine (Hcy) and methionine (Met). Homocystinuric patients present a variable degree of neurological dysfunction whose pathophysiology is poorly understood. In the present study, we investigated the in vitro effect of Hcy and Met on some parameters of energy metabolism in hippocampus of rats. CO(2) production from [U-14C] acetate, glucose uptake and lactate release were assessed by incubating hippocampus prisms from 28-day-old rats in Krebs-Ringer bicarbonate buffer, pH 7.4, in the absence (controls) or presence of Hcy (10-500 microM) or Met (0.2-2.0mM). Hcy and Met decreased CO(2) production in a dose-dependent manner and increased lactate release. In contrast, glucose uptake was not altered by the metabolites. The effect of Hcy and Met on cytochrome c oxidase activity was also studied. It was observed that Met did not alter this enzyme activity, in contrast with Hcy, which significantly inhibited cytochrome c oxidase activity. It is suggested that impairment of brain energy metabolism caused by the metabolites accumulating in homocystinuria may be related to the neurological symptoms present in homocystinuric patients.
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, RS, Porto Alegre, Brazil.
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.forename: Débora
authors.initials: D
authors.lastname: Delwing
authors.forename: Bárbara
authors.initials: B
authors.lastname: Tagliari
authors.forename: Cristiane
authors.initials: C
authors.lastname: Matté
authors.forename: Clóvis M D
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D006712:Homocystinuria / Q000378:metabolism*; D008715:Methionine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006710:Homocysteine; D002245:Carbon Dioxide; D008715:Methionine; D003576:Electron Transport Complex IV; D005947:Glucose