| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Long-chain acyl-CoA thioesterases include a number of enzymes that catalyze the hydrolysis of fatty acyl-CoA thioesters to the corresponding free fatty acids and coenzyme A.It has been well documented that there is a markedly high level of hydrolytic activity toward long-chain acyl-CoAs in the brains of mammals, suggesting some specific role of the enzyme in this tissue. However, its physiological significance has remained unclear. In previous studies, we purified and characterized an enzyme, referred to as BACH (brain acyl-CoA hydrolase), from rat brain cytosol, and identified it as a novel long-chain acyl-CoA thioesterase by the cDNA cloning and sequence analysis. In rats, BACH was present at high levels both in the brain and testis, and accounted for the most part of palmitoyl-CoA hydrolyzing activities found there. In this study to gain an insight into physiological function of BACH, we investigated 1. Characteristics of human BACH and its gene structure ; 2. Mechanism of human BACH gene expression ; 3. Structural organization of mouse BACH gene ; 4. Tissue distribution of BACH in the mouse ; 5. Establishment of BACH gene-transfected cell lines ; and 6. Gene targeting. The findings obtained were very informative to understand biochemical and molecular biological properties of BACH, including catalytic and molecular properties, tissue and subcellular distribution, isoform formation, genomic organization, and transcriptional regulation. For further studies of BACH function, useful means were also provided. Thus, the present study will make a large contribution for a better understanding of physiological significance of BACH and probably this class of thioesterases.
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