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Research for the Inhibitor of Cholesterol Biosynthesis with the aid of Morus alba Callus Cultures

桑树愈伤组织培养物中胆固醇生物合成抑制剂的研究

基本信息

批准号：
06672116
负责人：
NOMURA Taro
金额：
$ 1.34万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672116/
关键词：
Morus alba Callus Cultures Isoprenoid Biosynthesis HMG CoA reductase Compactin beta-Sitosterol Isoprenylated phenol Cholesterol Hypercholesteremia イソプレノイド生合成 Morus alba カルスメバロン酸生合成 HMG-COA還元酵素阻害剤

项目摘要

Morus alba Cell cultures have at least two isoprenoid biosynthetic pathways, one of which is that for isoprenylated phenols and the other is that for sterols. In the administration of experiment with compactin, a potential 3-hydroxy 3-methylglutaryl CoA (HMG CoA) reductase inhibitor, to the M.alba cell cultures, the biosynthesis of the isoprene unit of the isoprenylated phenol was not affected by compactin, while the biosynthesis of the isoprene unit of beta-sitosterol from acetate was inhibited. This result suggests that compactin is a specific inhibitor of sterol biosynthesis from acetate origin. This work thus indicates the occurrence of at least two isoprenoid biosynthetic pathways, one of which is susceptible to compactin and the other resistant to compactin in M.alba cell cultures. In the previous experiment with [2-^<13>C] acetate, it has been found that the tricarboxylic acid (TCA) cycle participates in the biosynthesis of the isoprene unit of the isoprenylated phenol in M.alba cell cultures. In the administration of [2-^<13>C] acetic acid N-acetylcysteamine thioester to the cell cultures, the acetate precursor was intact into the isoprene unit of the isoprenylated phenol without the participation of the TCA cycle.On the other hand, the isoprenylated phenols in the cell cultures are biosynthesized from cinnamoylpolyketide intermediate. Simultaneous administration of ^<13>C-labeled L-phenylalanine and L-tyrosine as well as administration of ^<13>-labeled cinnamic acid N-acetylcysteamine thioester derivative to the M.alba cell cultures gave a conclusive evidence for the two independent pathways leading to p-coumaroyl CoA.One is pathway from L-phenylalanine to p-coumaroyl CoA by way of cinnamoyl CoA and the other is pathway from L-tyrosine to p-coumaroyl CoA through the deamination reaction.

桑树细胞培养物具有至少两个类异戊二烯生物合成途径，其中一个是异戊二烯化酚的途径，另一个是甾醇的途径。在将潜在的3-羟基3-甲基戊二酰辅酶A（HMG CoA）还原酶抑制剂康帕汀（compactin）施用至M.alba细胞培养物的实验中，异戊二烯化苯酚的异戊二烯单元的生物合成不受康帕汀的影响，而从乙酸酯合成β-谷甾醇的异戊二烯单元的生物合成受到抑制。这一结果表明，康伐他汀是一种特异性抑制剂的甾醇生物合成从乙酸来源。因此，这项工作表明至少有两个类异戊二烯生物合成途径的发生，其中一个是敏感的compactin和其他抗compactin在M.alba细胞培养。在先前使用[2- 1C<13>]乙酸酯的实验中，已经发现三羧酸（TCA）循环参与了白木霉细胞培养物中异戊二烯化苯酚的异戊二烯单元的生物合成。在将[2-^<13>C]乙酸N-乙酰基半胱胺硫酯给予细胞培养物时，乙酸酯前体完整地进入异戊二烯化苯酚的异戊二烯单元中，而没有TCA循环的参与。同时给予β<13>-C-标记的L-苯丙氨酸和L-酪氨酸以及β<13>-标记的肉桂酸N-乙酰基半胱胺硫酯衍生物，对M.alba细胞培养提供了两条独立的途径的确凿证据，一条是通过肉桂酰CoA从L-苯丙氨酸到p-香豆酰CoA的途径，另一条是通过脱氨基反应从L-酪氨酸到p-香豆酰CoA的途径。