Premium
Effect of methylmalonate on in vitro lactate release and carbon dioxide production by brain of suckling rats
Author(s) -
Wajner M.,
Dutra J. C.,
Cardoso S. E.,
Wannmacher C. M. D.,
Motta E. R.
Publication year - 1992
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01800350
Subject(s) - bicarbonate , methylmalonic acidemia , chemistry , incubation , in vitro , carbon dioxide , pathophysiology , medicine , endocrinology , biochemistry , organic chemistry
Summary Methylmalonate (MMA) accumulates in the tissues of patients with methylmalonic acidaemia, who present severe neurological signs soon after birth and later mental retardation. Attempting to understand the pathophysiology of the disorder, we investigated the effects of MMA on brain glucose uptake, lactate release and CO 2 production. Glucose uptake and lactate release were studied by incubating 40 µm wide brain prisms from 15‐day‐old rats in Krebs‐Ringer bicarbonate buffer, pH 7.0, containing 5.0 mmol/L glucose and one of three concentrations of MMA (1.0, 2.5 and 5.0 mmol/L). Controls did not contain MMA in the incubation medium. MMA induced a significant increase of lactate production in a dose‐dependent pattern that was proportional to glucose uptake by the brain prisms. We also studied the influence of MMA on brain CO 2 production from [2‐ 14 C]glucose and [U‐ 14 C]acetate by incubating brain prisms in the same buffer in the presence of the substrates with (experimental groups) or without (controls) 5.0 mmol/L MMA. MMA significantly reduced CO 2 formation from both substrates.