Metabolic Brain Disease

, Volume 9, Issue 1, pp 43–51 | Cite as

Regional amino acid neurotransmitter changes in brains of spf/Y mice with congenital ornithine transcarbamylase deficiency

  • L. Ratnakumari
  • Ijaz A. Qureshi
  • Roger F. Butterworth
Original Contributions


Congenital deficiencies of the urea cycle enzyme ornithine transcarbamylase (OTC) result in chronic hyperammonemia and severe neurological dysfunction including seizures and mental retardation. As part of a series of studies to elucidate the pathophysiologic mechanisms responsible for the CNS consequences of OTC deficiency, concentrations of ammonia-related and neurotransmitter amino acids were measured as their o-phthalaldehyde derivatives using high performance liquid chromatography with fluorescence detection in regions of the brains of sparse-fur (spf) mice, a mutant with an X-linked inherited defect of OTC. Compared to CD-1/Y controls, the brains of spf/Y mutant mice contained significant alterations of several amino acids. A generalized, up to 2-fold, increase of brain glutamine was observed, consistent with the exposure of these brains to increased concentrations of ammonia. Significant increases of brain alanine were also observed and, together with previous reports of increased concentrations of α-ketoglutarate, are consistent with ammonia-induced inhibition of α-ketoglutarate dehydrogenase in the brains of spf/Y mice. Increased brain content of the excitatory amino acid aspartate coul be responsible for the seizures frequently encountered in congenital OTC deficiency.

Key words

Ornithine transcarbamylase deficiency congenital hyperammonemia sparse-fur (spf) mouse cerebral amino acids seizures 


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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • L. Ratnakumari
    • 1
    • 2
  • Ijaz A. Qureshi
    • 1
  • Roger F. Butterworth
    • 2
  1. 1.Service of Medical GeneticsHôpital Ste-JustineMontreal
  2. 2.Neuroscience Research UnitHôpital St-Luc (Univ. Montreal)MontrealCanada

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