NDLI: Effect of α-Ketoisocaproate and Leucine on the in Vivo Oxidation of Glutamate and Glutamine in the Rat Brain

Content Provider	Springer Nature Link
Author	Zielke, H. Ronald Huang, Yinyin Baab, Peter J. Collins, Roger M. Zielke, Carol L. Tildon, J. Tyson
Copyright Year	1997
Abstract	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-$^{14}$C]glutamate and L-[U-$^{14}$C]glutamine in the brain were determined in the non-anesthetized rat. $^{14}$CO$_{2}$ generated by the metabolic oxidation of [$^{l4}$C]glutamate and [$^{14}$C]glutamine in brain was measured following its diffusion into the eluant during the microdialysis. Leucine and α-KIC exhibited differential effects on $^{14}$CO$_{2}$ generation from radioactive glutamate or glutamine. Infusion of 0.5 mM α-KIC increased [$^{l4}$C]glutamate oxidation approximately 2-fold; higher concentrations of α-KIC did not further stimulate [$^{14}$C]glutamate oxidation. The enhanced oxidation of [$^{14}$C]glutamate may be attributed to the function of α-KIC as a nitrogen acceptor from [$^{14}$C]glutamate yielding [$^{14}$C]α-ketoglutarate, an intermediate of the tricarboxylic acid cycle. [$^{14}$C-]glutamine oxidation was not stimulated as much as [$^{14}$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 [$^{14}$C]glutamate or [$^{14}$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.
Starting Page	1159
Ending Page	1164
Page Count	6
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	22
Issue Number	9
e-ISSN	15736903
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1997-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurosciences Neurology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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