1989 Fiscal Year Final Research Report Summary
Molecular biological study on the regulation of fatty acid biosynthesis
| Project/Area Number |
63570126
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
TANABE Tadashi National Cardiovascular Center Research Institute, Department of Parmacology, Director, 薬理部, 部長 (60025624)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAI Toshiyuki Okayama University, Faculty of Engineering Lecturer, 工学部, 講師 (20187917)
YOKOYAMA Chieko National Cardiovascular Center Research Institute, Department of Parmacology, Re, 薬理部, 室員 (90200914)
IMADA Masaru Meiji Institute of Health Science, Division of Cell Biology Laboratory Chief
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| Project Period (FY) |
1988 – 1989
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| Keywords | Fatty acid biosynthesis / Metabolic regulation / Acetyl-CoA carboxylase / Biotin / mRNA |
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| Research Abstract |
Fatty acids are essential substance for organisms as membrane components, energy sources etc. Accumulation of fatty acids, however, causes various cardiovascular diseases and obesity. In the present study we have investigated the regulatory mechanism of fatty acid biosynthesis to overcome these diseases. According to the previous study by our and other groups, biosynthesis of fatty acid is regulated by modulating the activity of acetyl-CoA carboxylase (ACC). Following results have been obtained by the present study.
1. With use of our cDNA clones of chicken liver ACC as probes and specific antibodies, expression of ACC was studied. ACC mRNA and the enzyme protein was found in liver, brain, testis, kidney, lung and heart. The changes of the hepatic and heart contents of ACC mRNA and the enzyme protein in growing chicks were measured. In the post-hatching period, the bepatic mRNA markedly increased at least 70- fold when compared to that before hatching. This increase was not observed in
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chicks receiving no diet These changes were closely paralleled with the rise of the hepatic content of ACC protein in chicks up to 10 days old. Contents of ACC mRNA and the enzyme protein in heart were not changed during development.
2. Primary structure of various biotin-dependent carboxylase including chicken and rat liver ACC was compared and a genealogical tree was constructed. The results indicated the animal ACC, a multifunctional polypeptide has been formed by gene fusion of monofunctional polypeptide chains found in Escherichia coli ACC during molecular evolution. The result is completely agreed with the previous enzymological observations of biotin-dependent enzymes.
3. Cloning of ACC gene has been attempted by screening human genomic libraries with chicken ACC cDNA as a probe and the obtained colones covered approximately 40 kb of the gene. The 13.4 kb-region of the gene was characterized. The 404 residues of the protein-coding region determined was distributed into 4 exons. The deduced primary structure of human ACC coincided with that of chicken and rat enzymes in 95 and 98 %, respectively. Cloning and characterization of the remaining portion of the gene are now in progress. Less
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