Analysis of Brain Fatty Acid Metabolism and its Abnormality by Application of Monoclonal Antibody

点击翻译按钮获取中文摘要

In the present project, weinvestigated reaction systems of long- and very- long-chaine fatty acid elongation in detail. We prepared monoclonal antibodies for the enzymes and cytochromes involved in the elongation system, and investigated their application of the analysis of fatty acid metabolise and its abnormality in brain. The major results obtained are:1) We decided the cDNA nucleotide sequence of NADH-cytochrome b_5 reductase which was involved in fatty acid elongation. We obtained monoclonal antibody possessing high titer for the reductase.2) Computer simulation analysis revealed that the existence of wto parallel pathways in the very-long-chain fatty acid elongation in brain microsomes.3) At least two separate condensing snzymes were involved in the elongation depending on the chain length of fatty acids.4) In the elongation of arachidoyl-CoA and arachidonoyl-CoA condensation reaction waw evidenced to be rate limiting, and stereospecific S-sydrogen from NADPH was transfered in the reduction step.5) We found an elongation condition to produce 26:0 and 26:1, which have been produced specifically in adrenoleukodystrophy patients. These results will give an approch for the cause and process of the demyelinationg disease.