Branched‐chain amino acids and neurotransmitter metabolism: Expression of cytosolic branched‐chain aminotransferase (BCATc) in the cerebellum and hippocampus

Abstract

In the brain, catabolism of the branched-chain amino acids (BCAAs) provides nitrogen for the synthesis of glutamate and glutamine. Glutamate is formed through transfer of an amino group from BCAA to alpha-ketoglutarate in reaction catalyzed by branched-chain aminotransferases (BCAT). There are two isozymes of BCAT: cytosolic BCATc, which is found in the nervous system, ovary, and placenta, and mitochondrial BCATm, which is found in all organs except rat liver. In cell culture systems, BCATc is found only in neurons and developing oligodendrocytes, whereas BCATm is the isoform in astroglia. In this study, we used immunohistochemistry to examine the distribution of BCATc in the rat brain, focusing on the well-known neural architecture of the cerebellum and hippocampus. We show that BCATc is expressed only in neurons in the adult rat brain. In glutamatergic neurons such as granule cells of the cerebellar cortex and of the dentate gyrus, BCATc is localized to axons and nerve terminals. In contrast, in GABAergic neurons such as cerebellar Purkinje cells and hippocampal pyramidal basket cells, BCATc is concentrated in cell bodies. A common function for BCATc in these neurotransmitter systems may be to modulate amounts of glutamate available either for release as neurotransmitter or for use as precursor for synthesis of GABA. Particularly striking in our findings is the strong expression of BCATc in the mossy fiber pathway of the hippocampal formation. This result is discussed in light of the effectiveness of the anticonvulsant drug gabapentin, which is a specific inhibitor of BCATc.

Dietary branched chain amino acids ameliorate injury-induced cognitive impairment

“…The transamination of α-ketoglutarate to glutamate using BCAA-derived nitrogen occurs despite the diminution of BCATc expression. However, as BCATc is found primarily in the synaptic terminals (27), and it is not the ratelimiting step in BCAA metabolism, it is ideally positioned to use exogenous BCAAs for the synthesis of glutamate.…”

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

“…In the present study, we identified (with at least 3 peptides) 23 proteins with significantly increased (Table 1) and 23 proteins with decreased ( Table 2) (1) - (Chihara et al, 2007), (2) - (Folci et al, 2014), (3) - (Chen et al, 2002), (4) - (Tanaka et al, 2000), (5) - (Ding and Shen, 2008), (6) - (Na et al, 2012), (7) - (Lyon et al, 2007), (8) - (Sweatt et al, 2004), (9) - (Bahn et al, 2002), (10) - (Manya et al, 1998), (11) - (Kamada et al, 2003), (12) - (McKenna et al, 2000), (13) - (Christel et al, 2012), (GO) -According to Gene Ontology database. …”

“…BCAT1 is localized exclusively in neurons in the adult rat brain and catalyzes the reversible transamination of α-ketoglutarate to glutamate while GAD catalyzes the decarboxylation of glutamate to GABA (Sweatt et al, 2004). GABA degradation has an important role in glutamate-and GABA-erg balance and generates succinic semialdehyde (SSA) intermediate via the activation of GABA transaminase (GABA-T).…”

Cytosolic Branched Chain Aminotransferase (BCATc) Regulates mTORC1 Signaling and Glycolytic Metabolism in CD4+ T Cells

“…For detection of phospho-E1␣, E1␣, and E2, an anti-E1␣ pS293, an anti-E2, and an E1␣ peptide antibody (27) were used. BCAT isozyme-specific antisera were raised in rabbits using purified recombinant human BCATm and BCATc and affinity purified as described (8,24). CsA was purchased from Enzo Life Sciences (Farmingdale, NY) and dissolved in dimethyl sulfoxide, rapamycin was purchased from LC Laboratories (Woburn, MA), NALA was purchased from BACHEM (Bubendorf, Switzerland).…”