Involvement of branched-chain amino acid aminotransferase (Bcat1/Eca39) inapoptosis

The branched-chain amino acid aminotransferase, Bcat1/Eca39, catalyzes the first step of branched-chain amino acid catabolism. Bcat1/Eca39 was origina lly isolated from a c-myc-induced tumor and was proven to be a direct targe t for c-Myc regulation. The gene is highly conserved in evolution and disru ption of its yeast homolog affects cell growth. To assess the role of Bcat1 /Eca39 in mammalian cells, we overexpressed Bcat1/Eca39 in murine cells and studied effects on cell growth. Overexpression of Bcat1/Eca39 had no appar ent effect on the proliferation of cells grown with high serum concentratio ns, but under serum deprivation conditions, led to a decrease in cell viabi lity. Cell death under these conditions displayed apoptotic features. The b ranched-chain keto acid, alpha-ketoisocaproate, a metabolite of leucine cat abolism produced by BCAT1/ECA39, was previously found to inhibit cell growt h. We show that a-ketoisocaproate can induce rapid apoptotic cell death, Th is observation suggests that the growth inhibitory effect of BCAT1/ECA39 an d its apoptosis promoting effect may be mediated by the levels of the produ cts of BCAT1/ECA39 activity, namely, branched-chain keto acids, (C) 1999 Fe deration of European Biochemical Societies.