PORPHYRINS AND QUINONES AS ENZYME COFACTORS

描述：在人类和动物中，血红素从血红蛋白中释放出来， 肌红蛋白，细胞色素P-450降解转化为开链 胆绿素的血红素加氧酶(HO)催化。在这些依赖氧气的环境中 过程中，一氧化碳被释放出来。在大脑中发现HO活性 组织暗示一氧化碳是一种神经递质。一氧化氮合酶 (一氧化氮合酶)还通过催化生成双原子气体分子 L精氨酸转化为瓜氨酸，产物NO是主要 神经、免疫和心血管系统的调节器。一个目标 这项研究项目的重点是阐明O2-的化学 野生动物体内血红素辅因子的激活及其催化机制 HO和NOS以及用定点突变制备的酶 探测血红素结构和活性的变化。实现这一目标的途径 项目是表征含氧和氧化的中间体 通过振动光谱学的血红素辅助因子，再加上一个有力的 使用新型、高保护金属卟啉的合成模型方法 这甚至可以在室温下稳定Fe-O2加合物。呼吸- 所有有氧生命形式中的耦合能量传递都是通过 细胞色素氧化酶。大肠杆菌的细胞色素BD氧化酶是一种末端 一种酶，其异常高的O2亲和力与其数据有关 辅因子，一种5，6-二羟基原氯。氢化卟啉的研究 将继续使用发色团特定的技术 共振拉曼光谱。一个主要目标是确定 辅因子的轴向配体。对于氯素d，这项工作旨在 确认这一辅因因缺乏强大的 轴向配体。D辅因子的化学工作将得到支持。 通过一种新的有效的综合模型。第三个方面，也是不断扩大的 本研究项目是对苯二酚的作用进行研究。 胺氧化酶中的辅因子。与孔雀一样，这项工作依赖于 准确的苯二酚模型化合物，用于光谱比较。 结缔组织的交联剂是由铜来实现的 氧化酶是一种活性部位含有酪氨酸衍生的苯二酚的酶。 拟议中的研究将使用拉曼光谱来鉴定性质 以前未表征的辅因子中的苯醌取代基(如 在催化循环的中间产物中，以及在 辅因子的生物合成。

DESCRIPTION: In humans and animals, the heme released from hemoglobin, myoglobin, and cytochrome P-450 degradation is converted to open-chain biliverdin by heme oxygenase (HO) catalysis. In these O2-dependent processes, carbon monoxide is released. HO activity found in brain tissue has implicated CO as a neurotransmitter. Nitric oxide synthase (NOS) also generates a diatomic gas molecule by catalyzing the conversion of L-arginine to citrulline, and the product NO is a major regulator in the nervous, immune, and cardiovascular systems. A target of this research project is the elucidation of the chemistry of O2- activation and the mechanism of catalysis of the heme cofactors in wild- type HO and NOS and in enzyme prepared with site-directed mutations that probe changes in heme structure and activity. The approaches of this project are to characterize oxygenated and oxidized intermediates of the heme cofactors by vibrational spectroscopy, coupled with a vigorous synthetic model approach using novel, highly protected metallo-porphyrins that even stabilize an Fe-O2 adduct at room temperature. Respiration- coupled energy transduction in all aerobic life forms is carried out by cytochrome oxidases. Cytochrome bd oxidase of E. coli is a terminal oxidase whose unusually high O2 affinity is associated with its d cofactor, a 5,6- dihydroxyprotochlorin. Research on this hydroporphyrin oxidase will be continued using the chromophore-specific technique of resonance Raman spectroscopy. A principal goal is the identification of the axial ligands of the cofactors. For chlorin d, this work seeks to confirm the proposal that this cofactor is unique in lacking a strong axial ligand. Work on the chemistry of the d cofactor will be supported by a new effective synthetic model. A third and expanding aspect of this research project is the investigation of the role of quinone cofactors in amine oxidase. As with the porhyrins, this work relies on accurate quinone model compounds for spectroscopic comparison. Crosslinking of connective tissue is carried out by copper lysil oxidase, an enzyme with a tyrosine-derived quinone at its active site. The proposed research will use Raman spectroscopy to identify the nature of quinone substituents in previously uncharacterized cofactors (as in lysil oxidase), in intermediates of the catalytic cycle, and during the biosynthesis of the cofactor.