Glucose metabolism after traumatic brain injury: estimation of pyruvate carboxylase and pyruvate dehydrogenase flux by mass isotopomer analysis.
The metabolism of [1, 2 (13)C(2)] glucose via the tricarboxylic acid (TCA) cycle yields a number of key glutamate mass isotopomers whose formation is a function of pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH). Analysis of the isotopomer distribution patterns was used to determine the relative flux of glucose entry into the TCA cycle through anaplerotic and oxidative pathways in the cerebral cortex of both uninjured and traumatically injured adult male rats. In the cerebral cortex of uninjured animals the PC/PDH ratio showed greater metabolism of glucose via pyruvate carboxylase, which is consistent with the notion that the majority of glucose taken up at rest is used as a substrate for anaplerotic processes and not as an energy source. While traumatic brain injury did not change the overall (13)C enrichment of glutamate indicating a continued oxidation of glucose, the PC/PDH ratio was reduced in the injured cortex at 3.5 h after injury. This suggests that glucose metabolism is primarily directed through pathways associated with energy production in the early postinjury period. By 24 h, the anaplerotic flux decreased and the PC/PDH ratio increased in both the injured and non-injured cortex indicating a switch away from energy production to pathways associated with anabolic and/or regenerative processes.
Bartnik
Brenda L
BL
Brain Injury Research Center, Division of Neurosurgery, Department of Surgery and David Geffen School of Medicine at UCLA, University of California-Los Angeles, CA, USA. bbgartnik@llu.edu
Hovda
David A
DA
Lee
Paul W N
PW
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002952:Citric Acid Cycle; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007554:Isotopes; D008297:Male; D010084:Oxidation-Reduction; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D007554:Isotopes; D011768:Pyruvate Dehydrogenase Complex; D018698:Glutamic Acid; D011766:Pyruvate Carboxylase; D005947:Glucose