Study on improving drug for hyperchoresterolemia directed by sterol biosynthesis in Morus alba cell cultures

Morus alba细胞和悬浮液文化产生的类固醇和同位素在高水平。在一个实验中，与[2-y-D113 y-D1C]乙酸盐的结合比较，将C-13与同位素的多甲苯、kuwanons J、Q、R和V，揭示了在C-13公司中减少的氧化程度。这一事实指的是较低羟基化合物的前生物合成，Kwanon V，随后是以Kwanon R和随后Kwanon J的成功羟基化反应。它还建议，糖基吗啡是以同样的方式从多伯罗富兰E的生物合成。M.阿尔巴细胞文化中有两种独立的同位素生物合成物，一种是对compactin （ML-236 B）敏感的，一种是对HMG-CoA还原酶的抑制剂，另一种是不敏感的。在两种异丁二烯生物合成中，非敏感性的、结合的乙酸酯不是直接的乙酸酯管理员，而是通过三氯酸循环（TCA循环）重建的乙酸酯。为了测试在异丁二烯生物合成中参与TCA循环的情况，脂肪酸片段被调查。棕榈酸盐是从卡勒斯文化管理层分离出来的[2-伊D113伊D1C]乙酸盐。D113-D1C-NMR spectrum of the palmitate demonstrated that the specified positions corresponding to the methyl group of the acetate were labeled with C-13。这一事实提出了一项建议，即通过β-氧化物从脂肪酸中通过TCA循环将乙酸转化为同位素单元。这是脂肪酸对同种生物合成的贡献的第一个例子。这是根据脂肪酸生物合成法的一个重要因素，因为它在提高药物对高胆固醇的发展中也是一个重要的因素。

Morus alba cells and suspension cultures produce sterols and isoprenylated phenols in high yield. In the experiment with[2-ィイD113ィエD1C]acetate, comparison of incorporation of C-13 into polyketide moieties of isoprenylated phenols, kuwanons J, Q, R, and V, revealed that increasing of oxidation degrees decreased in corporation of C-13. This fact indicated that foremost biosynthesis of lesser hydroxylated compound, kuwanon V, followed by successive hydroxylation reactions to form kuwanon R and then kuwanon J. It was also suggested that chalco-moracin was biosynthesized from mulberrofuran E in the same way. There are two independent isoprene biosyntheses in M.alba cell cultures, one is sensitive to compactin (ML-236B), an inhibitor of HMG-CoA reductase, and the other is non-sensitive. In one of the two isoprene biosyntheses, non-sensitive to compactin, incorporated acetate was not intact acetate administered, but reconstructed acetate through tricarboxylic acid cycle (TCA cycle). To examine the participation of TCA cycle in the isoprene biosynthesis, fatty acid fraction was investigated. Palmitate was isolated from the callus cultures administered [2-ィイD113ィエD1C]acetate. The ィイD113ィエD1C-NMR spectrum of the palmitate demonstrated that the specified positions corresponding to the methyl group of the acetate were labeled with C-13. This fact suggested that the acetate from fatty acid through β-oxidation was incorporated into the isoprene unit via TCA cycle. This is the first example of contribution of fatty acid to the isoprene biosynthesis. It was thus indicated that fatty acid biosynthesis was also important factor in the development of improving drug for hyperchoresterolemia.