Metabolism of the Flavonol Kaempferol in Kidney Cells Liberates the B-ring to Enter Coenzyme Q Biosynthesis
Metabolism of the Flavonol Kaempferol in Kidney Cells Liberates the B-ring to Enter Coenzyme Q Biosynthesis
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DOI：
10.3390/molecules25132955
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发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Clarke, Catherine F.
中科院分区：
文献类型：
--
作者：
Fernandez-del-Rio, Lucia;Soubeyrand, Eric;Clarke, Catherine F.
辅酶Q（CoQ）是线粒体电子传递链的重要组成部分，也是存在于所有细胞膜中的重要抗氧化剂。辅酶Q缺乏症在衰老和与年龄相关的疾病中很常见，目前的治疗仅限于辅酶Q补充剂。依赖于辅酶Q补充剂的策略遭受这种非常疏水的分子的不良吸收和运输。在先前的研究中，膳食黄酮醇山奈酚被报道作为辅酶Q环前体并增加肾脏细胞中的辅酶Q含量，但既没有描述进入辅酶Q生物合成的分子部分，也没有描述其机制。本研究从紫茎泽兰属植物中分离得到了B环特异性标记的山奈酚。用这种化合物处理的肾细胞将山奈酚的B环并入新合成的辅酶Q中，表明B环通过植物细胞中描述的机制代谢。山奈酚是水果和蔬菜中存在的天然类黄酮，具有抗氧化、抗癌和抗炎治疗特性。更好地了解山奈酚作为辅酶Q环前体的作用，使这种生物活性化合物成为设计干预措施的潜在候选者，旨在增加内源性辅酶Q生物合成，并可能改善衰老和疾病中辅酶Q缺乏的表型。
Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an important antioxidant present in all cellular membranes. CoQ deficiencies are frequent in aging and in age-related diseases, and current treatments are limited to CoQ supplementation. Strategies that rely on CoQ supplementation suffer from poor uptake and trafficking of this very hydrophobic molecule. In a previous study, the dietary flavonol kaempferol was reported to serve as a CoQ ring precursor and to increase the CoQ content in kidney cells, but neither the part of the molecule entering CoQ biosynthesis nor the mechanism were described. In this study, kaempferol labeled specifically in the B-ring was isolated fromArabidopsisplants. Kidney cells treated with this compound incorporated the B-ring of kaempferol into newly synthesized CoQ, suggesting that the B-ring is metabolized via a mechanism described in plant cells. Kaempferol is a natural flavonoid present in fruits and vegetables and possesses antioxidant, anticancer, and anti-inflammatory therapeutic properties. A better understanding of the role of kaempferol as a CoQ ring precursor makes this bioactive compound a potential candidate for the design of interventions aiming to increase endogenous CoQ biosynthesis and may improve CoQ deficient phenotypes in aging and disease.