Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves.
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.
Sweatt
Andrew J
AJ
Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. asweatt@wfubmc.edu
Wood
Mac
M
Suryawan
Agus
A
Wallin
Reidar
R
Willingham
Mark C
MC
Hutson
Susan M
SM
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D004064:Digestive System / Q000166:cytology / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology*; D005260:Female; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000145:classification / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D000637:Transaminases / Q000145:classification / Q000378:metabolism*
D000597:Amino Acids, Branched-Chain; D007527:Isoenzymes; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000637:Transaminases; C019798:branched-chain-amino-acid transaminase