PHYTOL METABOLITES ARE DIETARY FACTORS THAT ACTIVATE THE NUCLEAR RECEPTOR RXR

RXR是一种核受体， 在细胞信号传导中起着核心作用， 受体。以前，9-顺式视黄酸是从氯仿 牛血清提取物， 转录活性质谱分析的材料， 活性组分为饱和二萜酸， 诱导RXR依赖性转录的浓度在4 和64 μ M。虽然比植烷酸强200倍， 9 cRA在等量浸提液中无法检测到， 存在于可以解释活性的浓度。 合成了另一种植醇代谢产物植烯酸， 具有与植烷类似的效力和功效的刺激RXR 酸这些代谢物特异性地从[3 H]-9cRA置换 RXR的k1值为4 μ M，表明它们的转录 作用是由直接受体相互作用介导的。植醇 代谢物是生理效应物的引人注目的候选物， 因为它们的RXR结合亲和力和激活效力匹配 微摩尔循环浓度。鉴于他们的独家 饮食来源，这些叶绿素代谢物可能代表了必需的 通过调节细胞代谢的营养素 RXR依赖的信号通路。这一假设被 通过比较用植烷素喂养的老鼠的生长情况， 缺酸饮食，动物组饲喂补充 植烷酸总之，这些发现使我们提出 叶绿醇代谢物可能是连接植物的营养信号， 动物的饮食状态与各种内分泌和内分泌 通过核受体RXR的信号通路。

Summary of Work: RXR is a nuclear receptor which plays a central role in cell signalling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid was from chloroform extracts of bovine serum by following RXR-dependent transcriptional activity. Mass spectrometric analyses of material in active fractions pointed to the saturated diterpenoid acid, which induced RXR-dependent transcription at concentrations between 4 and 64 uM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytenic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with k1 values of 4 uM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signalling pathways. This hypothesis is being tested by comparing the growth of rats raised on phytanic acid-deficient diets with groups of animals fed diets supplemented with phytanic acid. In summary, these findings lead us to propose that phytol metabolites may be nutritional signals linking the animal's dietary state with a variety of endocrine and intracrine signalling pathways through the nuclear receptor RXR.