Elevation of amino acids in the interstitial space of the rat brain following infusion of large neutral amino and keto acids by microdialysis: alpha-ketoisocaproate infusion.

alpha-Ketoisocaproate was infused into the brain of free-moving, awake rats by microdialysis to create a microenvironment similar to that found in maple syrup urine disease. The eluate of the probe was analyzed for amino acids to determine if alpha-ketoisocaproate was transaminated to leucine and if the amino acid homeostasis was altered. The interstitial levels of leucine were increased up to 11-fold and other large neutral amino acids were increased 2- to 3-fold indicating an active branched chain keto acid transaminase activity and enhanced hetero-exchange across cell membranes. The elevation of large neutral amino acids in the interstitial space is discussed in terms of the synthesis of leucine and neurotransmitters in maple syrup urine disease.