PMID: 2502068Aug 1, 1989Paper

Changes in urea cycle-related metabolites in the mouse after combined administration of valproic acid and an amino acid load

Archives of Biochemistry and Biophysics
E AlonsoV Rubio

Abstract

Increased blood ammonia was induced in fasting mice by ip administration of 200 mg/kg Na-valproate followed 1 h later by 13 and 4 mmol/kg alanine and ornithine, respectively. When valproate was not used blood or liver ammonia was not increased, but increases were observed in liver glutamate (5-fold), glutamine (2-fold), aspartate (5-fold), acetylglutamate (15-fold), citrulline (35-fold), argininosuccinate (11-fold), arginine (11-fold), and urea (3-fold). The level of carbamoyl phosphate (less than 2 nmol/g) was, by far, the lowest of all urea cycle intermediates. The large increase in citrulline indicates that argininosuccinate synthesis was limiting, and that the increase in acetylglutamate induced a considerable activation of carbamoyl phosphate synthetase, which agrees with theoretical expectations, irrespective of the actual KD value for acetylglutamate. Pretreatment with valproate resulted in lower hepatic levels of glutamate, glutamine, aspartate, acetyl-CoA, and acetylglutamate. At the level found of acetylglutamate the activation of carbamoyl phosphate synthetase would be expected to be similar to that without valproate. Indeed, the levels of citrulline were similar with or without valproate. Argininosuccinate, arginine...Continue Reading

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Citations

Jan 1, 1993·Journal of Inherited Metabolic Disease·M HoriuchiT Saheki
Jan 1, 1997·Life Sciences·J P Bolaños, J M Medina
Jan 19, 2008·Expert Opinion on Pharmacotherapy·Thorsten GerstnerStephan König
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Jun 22, 2006·Seizure : the Journal of the British Epilepsy Association·Thorsten GerstnerStephan A Koenig
May 12, 2007·Seizure : the Journal of the British Epilepsy Association·Thorsten GerstnerStephan A Koenig
Oct 23, 2009·Metabolism: Clinical and Experimental·Tuneyoshi KaTetsuya Yamamoto
Apr 1, 1997·Journal of Clinical Psychopharmacology·W C WirshingA Sun
Mar 1, 1991·Archives of Biochemistry and Biophysics·V FelipoS Grisolía
May 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·A Yingyu ZhouG Weihong Lu

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