Metabolism of Aromatic Ring Precursors in Coenzyme Q Biosynthesis

科学价值：碳水化合物（糖）或脂质（脂肪）的控制燃烧产生ATP，细胞的能量货币。辅酶Q（也称为泛醌，CoQ或Q）是一种产生ATP所必需的有机分子。CoQ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，CoQ分子有两个部分：(1)一个长碳包含“尾巴”，将其固定在膜上；(2)一个芳香环结构（苯醌），它的性质允许它运送电子和质子，这是它在ATP形成过程中必不可少的功能，也提供了它作为抗氧化剂功能所必需的氢原子。细胞通常被认为是由前体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CoQ生物形成的新途径，该途径来自对氨基苯甲酸（pABA），长期以来人们一直认为它专门用于叶酸的生物合成。有趣的是，与叶酸不同，CoQ的化学成分中不含氮。阐明含有氮的氨基被去除的生物步骤或序列是本项目的关键目标。新的证据表明，某些植物代谢物也可能作为CoQ的潜在环前体，这表明产生CoQ的途径甚至更多。该项目将研究这些新的可能途径，并确定它们是否在其他生物体中起作用。更广泛的影响：在这个项目中，研究生和本科生被训练成研究人员，研究生也接受科学艺术和教学方面的训练。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。学生们不再像以前那样学习课本上描述的必须死记硬背的代谢途径，而是认识到还有许多尚未解决的问题和其他途径有待发现。这导致他们质疑教科书的路径，并问：“我们怎么知道？”这些途径有何不同？为什么要有不止一条路径呢？”本科生，包括代表性不足的少数民族学生，学习表征突变，在代谢标记实验中使用同位素，在实验室中制备和分析脂质提取物，并在实践中学习科学。学生们还将看到，在有机合成化学、生物化学和细胞生物学方面具有跨学科专业知识的项目教师之间的跨学科互动如何推动科学研究。学生在本科生会议、加州大学洛杉矶分校专题讨论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。除了提高对必需分子CoQ生物合成的认识外，该结果还可能导致农业应用，因为该途径中涉及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.