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Journal of Inherited Metabolic Disease

, Volume 15, Issue 1, pp 92–96 | Cite as

Effect of methylmalonate onin vitro lactate release and carbon dioxide production by brain of suckling rats

  • M. Wajner
  • J. C. Dutra
  • S. E. Cardoso
  • C. M. D. Wannmacher
  • E. R. Motta
Article

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 CO2 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 CO2 production from [2-14C]glucose and [U-14C]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 CO2 formation from both substrates.

Keywords

Glucose Uptake Neurological Sign Lactate Production Bicarbonate Buffer Methylmalonic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© SSIEM and Kluwer Academic Publishers 1992

Authors and Affiliations

  • M. Wajner
    • 1
  • J. C. Dutra
    • 1
  • S. E. Cardoso
    • 1
  • C. M. D. Wannmacher
    • 1
  • E. R. Motta
    • 1
  1. 1.Departamento de BioquimicaInstituto de BiocienciasPorto Alegre, RSBrazil

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