Effect of [alpha]-Ketoisocaproate and Leucine on the in Vivo Oxidation of Glutamate and Glutamine in the Rat Brain

• Published in: Neurochemical research 1997-09, Vol.22 (9), p.1159
• Main Authors: Zielke, H Ronald, Huang, Yinyin, Baab, Peter J, Collins, Roger M, Zielke, Carol L, Tildon, J Tyson
• Format: Article
• Language: English
• Subjects: Oxidation
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1023/A:1027325620983

Leucine and α-ketoisocaproate (α-KIC) were perfused at increasing concentrations into rat brain hippocampus by microdialysis to mimic the conditions of maple syrup urine disease. The effects of elevated leucine or α-KIC on the oxidation of L-[U-^sup 14^C]glutamate and L-[U-^sup 14^C]glutamine in the brain were determined in the non-anesthetized rat. ^sup 14^CO^sub 2^ generated by the metabolic oxidation of [^sup l4^C]glutamate and [^sup 14^C]glutamine in brain was measured following its diffusion into the eluant during the microdialysis. Leucine and α-KIC exhibited differential effects on ^sup 14^CO^sub 2^ generation from radioactive glutamate or glutamine. Infusion of 0.5 mM α-KIC increased [^sup l4^C]glutamate oxidation approximately 2-fold; higher concentrations of α-KIC did not further stimulate [^sup 14^C]glutamate oxidation. The enhanced oxidation of [^sup 14^C]glutamate may be attributed to the function of α-KIC as a nitrogen acceptor from [^sup 14^C]glutamate yielding [^sup 14^C]α-ketoglutarate, an intermediate of the tricarboxylic acid cycle. [^sup 14^C-]glutamine oxidation was not stimulated as much as [^sup 14^C-]glutamate oxidation and only increased at 10 mM α-KIC reflecting the extra metabolic step required for its oxidative metabolism. In contrast, leucine had no effect on the oxidation of either [^sup 14^C]glutamate or [^sup 14^C]glutamine. In maple syrup urine disease elevated α-KIC may play a significant role in altered energy metabolism in brain while leucine may contribute to clinical manifestations of this disease in other ways.[PUBLICATION ABSTRACT]