Stimulation of coenzyme Q synthesis
Stimulation of coenzyme Q synthesis
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DOI：
10.1002/biof.5520320112
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发表时间：
2008-01-01
期刊：
影响因子：
6
通讯作者：
Dallner, Gustav
中科院分区：
文献类型：
--
作者：
Bentinger, Magnus;Tekle, Michael;Dallner, Gustav
膳食中辅酶Q （CoQ）进入器官的摄取是有限的，但也有一些例外，如肾上腺和卵巢。在缺乏条件下，刺激内源性合成可能是最佳解决方案。在啮齿类动物的运动中，低温暴露和一些物质在一定程度上提高了CoQ水平。对核受体PPAR α， RXR α和LXR α和β的研究并没有回答哪个核受体调节CoQ的生物合成的问题，目前我们还不能设计一个配体来上调CoQ的合成。在CoQ的紫外线照射下，形成了许多影响甲羟戊酸途径脂类合成的产物。其中确定了环氧化衍生物。对一系列类聚异戊二烯进行化学环氧化处理后发现，所有测试的聚顺式聚异戊二烯都没有任何影响，但一些全反式聚异戊二烯刺激了辅酶q的合成，在某些情况下还抑制了胆固醇的生物合成。生育三烯醇环氧化物被证明是非常有效的，那些在侧链上有一个环氧化物的CoQ合成增加了一倍或三倍，而那些有两个环氧化物的也抑制了50-90%的胆固醇合成。CoQ合成的升高是由生物合成酶mRNA水平升高引起的，而胆固醇合成的抑制点定位于氧化角鲨烯环化酶。
Uptake of dietary coenzyme Q (CoQ) into organs is limited but there are some exceptions such as adrenal glands and ovaries. Under deficient conditions an optimal solution could be stimulation of the endogenous synthesis. In rodent exercise, cold exposure and a few substances elevate the CoQ levels to some extent. Investigations of the nuclear receptors PPAR alpha, RXR alpha and LXR alpha and beta did not answer the question which nuclear receptor regulates CoQ biosynthesis and at present we cannot design a ligand for upregulation of the synthesis. Upon ultraviolet irradiation of CoQ a number of products are formed which influence the synthesis of the mevalonate pathway lipids. Among them epoxidated derivatives were identified. Upon chemical epoxidation of a series of polyisoprenoids it was found that none of the tested poly-cis polyisoprenols had any effect but some of the all-trans polyisoprenols stimulated CoQ synthesis and in some cases also inhibited cholesterol biosynthesis. Tocotrienol epoxides were proved to be very efficient, those having one epoxide in the side chain doubled or trebled the CoQ synthesis while those with two epoxides additionally also inhibited cholesterol synthesis by 50-90%. The elevation of CoQ synthesis was elicited by increased mRNA levels for biosynthetic enzymes while the inhibition point in the cholesterol synthesis was localized to oxidosqualene cyclase.