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Title: BRANCHED-CHAIN AMINO ACID CATABOLISM: UNIQUE SEGREGATION OF PATHWAY ENZYMES IN ORGAN SYSTEMS AND PERIPHERAL NERVES

Author
item SWEATT, ANDREW - WAKE FOREST UNIV MED SCH
item WOOD, MAC - WAKE FOREST UNIV MED SCH
item Suryawan, Agus
item WALLIN, REIDAR - WAKE FOREST UNIV MED SCH
item WILLINGHAM, MARK - WAKE FOREST UNIV MED SCH
item HUTSON, SUSAN - WAKE FOREST UNIV MED SCH

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/2003
Publication Date: 9/9/2003
Citation: Sweatt, A.J., Wood, M., Suryawan, A., Wallin, R., Willingham, M.C., Hutson, S.M. 2004. Branched-chain amino acid catabolism: Unique segregation of pathway enzymes in organ systems and peripheral nerves. American Journal of Physiology, Endocrinology, & Metabolism. 286(1):E64-E76.

Interpretive Summary: The purpose of this study was to find out the location of the first two enzymes that break down the branched-chain amino acid (BCAA) in the body. Using a technique called immunohistochemistry, we would be able to look at the location of these enzymes in the tissues of interest. Our results show that the first two enzymes, branched-chain aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD), is located in stomach, pancreas, uterus, testis, and kidney. The unique expression of these enzymes is consistent with their function of breaking down the BCAA for providing energy for the body.

Technical Abstract: We 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 alpha-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.