. Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves. Am J Physiol Endocrinol Metab 286: E64-E76, 2004. First published September 9, 2003 10.1152/ ajpendo.00276.2003We have examined the localization of the first two enzymes in the branched-chain amino acid (BCAA) catabolic pathway: the branched-chain aminotransferase (BCAT) isozymes (mitochondrial BCATm and cytosolic BCATc) and the branched-chain ␣-keto acid dehydrogenase (BCKD) enzyme complex. Antibodies specific for BCATm or BCATc were used to immunolocalize the respective isozymes in cryosections of rat tissues. BCATm was expressed in secretory epithelia throughout the digestive tract, with the most intense expression in the stomach. BCATm was also strongly expressed in secretory cells of the exocrine pancreas, uterus, and testis, as well as in the transporting epithelium of convoluted tubules in kidney. In muscle, BCATm was located in myofibrils. Liver, as predicted, was not immunoreactive for BCATm. Unexpectedly, BCATc was localized in elements of the autonomic innervation of the digestive tract, as well as in axons in the sciatic nerve. The distributions of BCATc and BCATm did not overlap. BCATm-expressing cells also expressed the second enzyme of the BCAA catabolic pathway, BCKD. In selected monkey and human tissues examined by immunoblot and/or immunohistochemistry, BCATm and BCATc were distributed in patterns very similar to those found in the rat. The results show that BCATm is in a position to regulate BCAA availability as protein precursors and anabolic signals in secretory portions of the digestive and other organ systems. The unique expression of BCATc in neurons of the peripheral nervous system, without coexpression of BCKD, raises new questions about the physiological function of this BCAT isozyme. digestive system; human; leucine; monkey; rat IN THE BODY, the nutritionally indispensable branched-chain amino acids (BCAAs) serve a number of important metabolic functions. BCAAs are key nitrogen donors for the synthesis of the metabolically significant dispensable amino acids glutamine and alanine. Glutamine is an important energy substrate for the gastrointestinal tract (38). Glutamine and alanine are also the major carriers of nitrogen from amino acid oxidation in skeletal muscle to the liver (7,20,33,48,56). In the central nervous system, BCAAs are thought to participate in an intercellular shuttle between neurons and astroglia that provides nitrogen for synthesis of the excitatory amino acid glutamate (3,4,31,39,40,64). In addition to the role of BCAAs in nitrogen metabolism, the BCAA leucine serves as an anabolic nutritional signal. Leucine stimulates protein synthesis in selected tissues via activation of the ribosomal protein S6 kinase 1 (12,19,42,61). Furthermore, high physiological concentrations of leucine stimulate secretion of insulin, and it has been postulated that this effect occurs in part via activation of glutamate dehydrogenase (43, 52).The initial reaction in the de...