Cellular Distribution of Branched-chain Amino Acid Aminotransferase Isoenzymes Among Rat Brain Glial Cells in Culture

Bixel, M. Gabriele; Hutson, Susan M.; Hamprecht, Bernd

doi:10.1177/002215549704500506

Cited by 79 publications

(109 citation statements)

References 46 publications

(33 reference statements)

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“…As reported previously (43), BCATm is not found in adult rat liver. The pattern of BCATm enzyme protein levels agrees with the reported distribution of BCATm activity in heart, kidney, and gastrocnemius (2,39,43). Measurement of BCATm in adipose tissue (corrected for protein loading) reveals levels of BCATm equivalent to those observed in kidney.…”

Section: Effects Of Chronic Leucine and Norleucine Supplementation Onsupporting

confidence: 86%

Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats

Lynch

Hutson

Patson

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Acute administration of leucine and norleucine activates the mammalian target of rapamycin (mTOR) cell-signaling pathway and increases rates of protein synthesis in a number of tissues in fasted rats. Although persistent stimulation of mTOR signaling is thought to increase protein synthetic capacity, little information is available concerning the effects of chronic administration of these agonists on protein synthesis, mTOR signal transduction, or leucine metabolism. Hence, we developed a model of chronic leucine/norleucine supplementation via drinking water and examined the effects of chronic (12 days) supplementation on protein synthesis in adipose tissue, kidney, heart, liver, and skeletal muscle from ad libitum-fed rats. The relative concentration of proteins involved in mTOR signaling and the two initial steps in leucine oxidation were also examined. Leucine or norleucine supplementation was accompanied by increased rates of protein synthesis in adipose tissue, liver, and skeletal muscle, but not in heart or kidney. Supplementation was not associated with increases in the anabolic hormones insulin or insulin-like growth factor I. Chronic supplementation did not cause apparent adaptation in either components of the mTOR cell-signaling pathway that respond to leucine (mTOR, ribosomal protein S6 kinase, and eukaryotic initiation factor 4E-binding protein-1) or the first two steps in leucine metabolism (the mitochondrial isoform of branched-chain amino acid transaminase, branched-chain keto acid dehydrogenase, and branched-chain keto acid dehydrogenase kinase), which may be involved in terminating the signal from leucine. These results suggest that provision of leucine or norleucine supplementation via the drinking water results in stimulation of postprandial protein synthesis in adipose tissue, skeletal muscle, and liver without notable adaptive changes in signaling proteins or metabolic enzymes.

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Section: Effects Of Chronic Leucine and Norleucine Supplementation Onsupporting

confidence: 86%

Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats

Lynch

Hutson

Patson

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

118

102

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“…Leucine readily passes into brain, where it is quickly transaminated to yield glutamate and 2-oxo-isocaproic acid (ketoleucine) (6,50,137). Magnetic resonance spectroscopy studies utilizing [ 15 N]leucine as a metabolic probe suggest that leucine is the source of as much as one-third of all brain nitrogen (52).…”

Section: Brain Handling Of Glutamatementioning

confidence: 99%

The Ketogenic Diet and Brain Metabolism of Amino Acids: Relationship to the Anticonvulsant Effect

et al. 2007

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In many epileptic patients, anticonvulsant drugs either fail adequately to control seizures or they cause serious side effects. An important adjunct to pharmacologic therapy is the ketogenic diet, which often improves seizure control, even in patients who respond poorly to medications. The mechanisms that explain the therapeutic effect are incompletely understood. Evidence points to an effect on brain handling of amino acids, especially glutamic acid, the major excitatory neurotransmitter of the central nervous system. The diet may limit the availability of oxaloacetate to the aspartate aminotransferase reaction, an important route of brain glutamate handling. As a result, more glutamate becomes accessible to the glutamate decarboxylase reaction to yield gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter and an important antiseizure agent. In addition, the ketogenic diet appears to favor the synthesis of glutamine, an essential precursor to GABA. This occurs both because ketone body carbon is metabolized to glutamine and because in ketosis there is increased consumption of acetate, which astrocytes in the brain quickly convert to glutamine. The ketogenic diet also may facilitate mechanisms by which the brain exports to blood compounds such as glutamine and alanine, in the process favoring the removal of glutamate carbon and nitrogen.

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“…Immunostaining of cell cultures derived from rat brain revealed that BCAT isozymes are differentially expressed, with BCATm expressed in astroglia and BCATc expressed in neurons (4,31,40). In contrast, BCKD appeared to be expressed in both cell types (3).…”

mentioning

confidence: 98%

“…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.…”

mentioning

confidence: 99%

Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves

Sweatt

Wood

Suryawan

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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140

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. 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...

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Cellular Distribution of Branched-chain Amino Acid Aminotransferase Isoenzymes Among Rat Brain Glial Cells in Culture

Cited by 79 publications

References 46 publications

Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats

Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats

The Ketogenic Diet and Brain Metabolism of Amino Acids: Relationship to the Anticonvulsant Effect

Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves

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