Metabolic Regulation in Fatty Acid Elongation System

微粒体脂肪酸延伸系统普遍存在于体细胞中。在神经系统中参与髓鞘形成。在血管系统中，该系统与动脉粥样硬化有关。延伸反应由四个步骤组成：缩合、第一还原、脱水和第二还原。缩合步骤被认为是限速步骤。第一个减少步骤也可能与监管有关。我们获得了以下与脂肪酸延伸调节有关的结果：1）我们发现SH试剂激活脂肪酸延伸，单烯脂肪酸抑制脂肪酸延伸。我们还发现jimpy小鼠脑内脂肪酸合成的减少，这种减少在缩合步骤中受到调节。2）分析了血管内脂肪酸伸长的调节机制。自发性高血压大鼠血管中脂肪酸的增加与高血压有关。3）从微粒体水平分析了白细胞和淋巴细胞中脂肪酸的延长。4）克隆了参与第二步2-酮脂酰辅酶A还原酶的NADH-细胞色素b_5还原酶，并采用定点突变的方法对其反应机理进行了分析。

The microsomal fatty acid elongation system is present ubiquitously in somatic cells. In nervous system it is involved in myilination. In vascular system the system is concemed with atheroscherosis. The elongation reaction consists of four steps:condensation, the first reduction; dehydration and the second reduction. The condensation step has been thought to be a rate limiting step. The first reduction step also possible to be related to regulation. We obtained the following recults in relation to the regulation of fatty acid elongation.1) We found an activation by SH-reagents and suppression by monoenoic fatty acids of fatty acid elongation. We also found the decrease of fatty acid synthesis in the brain of jimpy mouse and this was regulated in the condensation step.2) Regulation mechanism of fatty acid elongation in blood vessels has been analyzed. Invouement of fatty acid in blood vessels in terms of hypertension has been shown by wing spontaneously hypertensive rats.3) Fatty acid elongation in leukocytes and lymphocytes has been analyzed to the level of microsomes. The elongation of 20:0-CoA to 24:0 has been suggested to be distinct to the elongation to 22:0.4) The NADH-Cytochrome b_5 reductase which is involved in the second step 2-ketoacyl-CoA reductase has been cloaned and its reaction mechanism was analyzed by the method of site directed mutagenesis.