Disease relevance of BCAT1

• Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value: 90%) [1].
• ECA39 is a novel distant metastasis-related biomarker in colorectal cancer [1].

High impact information on BCAT1

• To understand the function of ECA39, we deleted the gene from the yeast genome [2].
• Disruption of ECA39 which is a recessive mutation that leads to a marked alteration in the cell cycle [2].
• Thus, C315 appears to be the sensor for redox regulation of BCAT activity, whereas C318 acts as the "resolving cysteine", allowing for reversible formation of a disulfide bond [3].
• The branched-chain keto acid, alpha-ketoisocaproate, a metabolite of leucine catabolism produced by BCAT1/ECA39, was previously found to inhibit cell growth [4].
• Involvement of branched-chain amino acid aminotransferase (Bcat1/Eca39) in apoptosis [4].

Biological context of BCAT1

• BCT1 assigned to chromosome 12 and BCT2 assigned to chromosome 19, were demonstrated to code for the expression of two molecular forms of BCT [5].
• Overexpression of Bcat1/Eca39 had no apparent effect on the proliferation of cells grown with high serum concentrations, but under serum deprivation conditions, led to a decrease in cell viability [4].
• FAGS analysis for GFP expression showed that BCAT transfection complexes yielded 1.6 more transfected cells and 20% higher log mean fluorescence than DCAT transfection complexes [6].

Anatomical context of BCAT1

• Our results suggest that the low BCATm mRNA level probably accounts for the low BCAT activity in sheep skeletal muscle, and that the metabolic scheme for branched-chain amino acid catabolism is specific to each species [7].
• Measurements of BCAT activity, mRNA and BCATm protein in sheep placenta and skeletal muscle revealed that BCATm is the sole BCAT isoenzyme expressed in placenta, whereas it contributes 57 and 71% of the BCAT activity in tensor fascia latae and masseter muscles from weaned lambs respectively [7].

Associations of BCAT1 with chemical compounds

• Finally, the structures reveal a unique role for cysteine residues in the mammalian BCAT [8].
• By comparing the rate of loss of absorbance at 340 nm in the modified spectrophotometric assay mixture containing leucine dehydrogenase to that obtained in the modified spectrophotometric assay mixture lacking leucine dehydrogenase, it is possible to measure BCAT activity in microliter amounts of rat tissue homogenates [9].
• Structure and bonding of transition metal-boryl compounds. Theoretical study of [(PH3)2(CO)ClOs-BR2] and [(PH3)2(CO)2ClOs-BR2] (BR2 = BH2, BF2, B(OH)2, B(OCH=CHO), Bcat) [10].
• The specific activities obtained by this procedure for the highly purified human mitochondrial and cytosolic isoforms of BCAT compare favorably with those obtained by a commonly used radiochemical procedure, which measures transamination between alpha-ketoiso[1-14C]valerate and L-isoleucine [9].
• Quantum chemical DFT calculations using the B3LYP functionals have been carried out for the electronically unsaturated 16 VE five-coordinate osmium boryl-complexes [(PH3)2(CO)ClOs-BR2] and the 18 VE six-coordinate complexes [(PH3)2(CO)2ClOs-BR2] with BR2 = BH2, BF2, B(OH)2, B(OHC=CHO), and Bcat (cat = catecholate O2C6H4) [10].

Other interactions of BCAT1

• Finally, the nomenclature BCAT1 for the cytosolic gene and BCAT2 for the mitochondrial BCAT gene is proposed [11].
• RESULTS: ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK [1].

Analytical, diagnostic and therapeutic context of BCAT1

• Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P<0.00001) [1].
• A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P<0.05) [1].
• CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine [1].
• Furthermore, circular dichroism spectra of recombinant human BCATm with liposomes showed that the commercial lipids used in the reconstituted transport assay contain BCAT amino acid substrates [12].

References