Metabolism of Aromatic Ring Precursors in Coenzyme Q Biosynthesis

科学价值：碳水化合物(糖)或脂类(脂肪)的受控燃烧会产生细胞的能量货币--三磷酸腺苷。辅酶Q(又称辅酶Q或辅酶Q)是一种生产三磷酸腺苷必不可少的有机分子。辅酶Q也是一种重要的抗氧化剂，可以保护细胞膜脂质免受自由基介导的损伤。从化学的角度来看，辅酶Q分子有两个部分：(1)一个长碳的“尾巴”，将它固定在膜上；(2)一个芳香环结构(苯二酚)，它的性质允许它传递形成ATP所必需的电子和质子，并提供作为抗氧化剂功能所必需的H原子。细胞通常被认为是从前体4-羟基苯甲酸(4-HB)产生苯醌环。研究人员发现了面包酵母中辅酶Q生物形成的一种新途径，这种途径来自对氨基苯甲酸或PABA，长期以来人们认为PABA专门用于叶酸的生物合成。有趣的是，与叶酸不同，辅酶Q的化学成分中不含氮。阐明去除含氮的氨基的生物学步骤或顺序是该项目的一个关键目标。新的证据表明，某些植物代谢物也可能是辅酶Q的潜在环前体，这表明有更多的途径生成辅酶Q。这个项目将调查这些新的可能的途径，并确定它们是否在其他组织中运作。广泛的影响：在这个项目中，研究生和本科生被培训为研究人员，研究生也接受艺术和科学教学方面的培训。研究生有机会教授和指导本科生，本科生是科学发现过程的积极参与者。学生们不是像以前教科书上描述的那样，学习必须记住的新陈代谢途径，而是学习到还有许多尚未解决的问题和其他尚未发现的途径。这让他们质疑课本上的路径，并问道：“我们怎么知道？这些路径有什么不同？为什么有不止一条路径？”本科生，包括未被充分代表的少数民族学生，学习表征突变体，在代谢标记实验中使用同位素，在实验室准备和分析脂肪提取物，并在实践中学习科学。学生们还将了解项目教员与有机合成化学、生物化学和细胞生物学的跨学科专业知识如何促进科学研究。学生在本科生会议、加州大学洛杉矶分校座谈会以及国内和国际会议上展示他们的研究成果。该项目确定了活细胞中能量产生过程所需的新途径。除了加强有关重要分子辅酶Q生物合成的知识外，结果还可能导致在农业上的应用，因为参与这一途径的酶是除草剂的潜在靶标。

Scientific Merit:The controlled burn of carbohydrates (sugars) or lipids (fat) generates ATP, the cell's energy currency. Coenzyme Q (also known as ubiquinone, CoQ or Q) is an organic molecule essential for production of ATP. CoQ is also a crucial antioxidant that can protect cell membrane lipids from damage mediated by free radicals. From a chemical standpoint, the CoQ molecule has two parts: (1) a long carbon containing "tail" that anchors it in the membrane, and (2) an aromatic ring structure (benzoquinone) with properties that allow it to ferry electrons and protons essential to its function in ATP formation, and also donate H atoms essential to its function as an antioxidant. Cells are generally thought to produce the benzoquinone ring from the precursor 4-hydroxybenzoic acid (4-HB). The investigators identified a new pathway for biological formation of CoQ in baker's yeast, emanating from para-aminobenzoic acid or pABA, long thought to be dedicated exclusively to the biosynthesis of folate. Interestingly, unlike folate, CoQ is devoid of nitrogen in its chemical composition. Elucidating the biological steps or sequence by which the amino group that contains the nitrogen is removed is a key goal of this project. New evidence indicates that certain plant metabolites may also serve as potential ring precursors of CoQ, suggesting there are even more routes to generate CoQ. This project will investigate these new possible pathways and also determine whether they operate in other organisms.Broader Impacts:In this project graduate and undergraduate students are trained as researchers, and graduate students are also trained in the art and teaching of science. Graduate students have the opportunity to teach and mentor undergraduate students, and undergraduate students are active participants in the scientific discovery process. Instead of learning about metabolism as previously characterized textbook pathways that must be memorized, students learn that there are many unsolved problems and other routes yet to be discovered. This leads them to question the textbook pathways, and ask, "How do we know? How do these pathways differ? Why have more than one pathway?". Undergraduate students, including underrepresented minority students, learn to characterize mutants, use isotopes in metabolic labeling experiments, and prepare and analyze lipid extracts in the laboratory and learn science by doing. Students also see how interdisciplinary interactions among the project faculty with interdisciplinary expertise in organic synthetic chemistry, biochemistry and cell biology advances scientific research. Students present their research findings at undergraduate conferences, UCLA symposia, and at national and international meetings. This project identifies new pathways required for energy generating processes in living cells. Besides enhancing knowledge regarding the biosynthesis of the essential molecule CoQ, results may also lead to applications in agriculture, as the enzymes involved in this pathway are potential targets for herbicides.