DIFFRACTION STUDIES OF THE BIOTIN VITAMERS

我们建议继续研究可能的反应物， 生物素介导的羧化反应的产物。 生物素是一种 维生素，作为一个强制性的辅因子，为主机 羧化酶和脱羧酶。 我们的研究将集中在 围绕着半反应机制的细节， 建议用于生物二氧化碳的吸收和转移 由这些酶催化。 我们的主要工具将是高 分辨率X射线衍射和量子化学技术，以及 这些将被用来研究电子，振动和 反应物和产物的几何性质以及 最有可能的反应途径。 我们的目标 是进一步完善这些技术并将其应用于生物素 大的问题。 作为副产品，我们期待新的方法 更强大，更简单的使用，并适合更广泛的 应用于生物学上有趣的问题。 生物素酶在代谢中起关键作用。 丙酮酸 羧化酶催化植物异生中的关键步骤。 乙酰辅酶A羧化酶在脂肪酸合成中起作用 合成. 其他生物素依赖性酶参与氨基 酸和嘌呤代谢。 主要证据是 所有的生物素酶以共同的机制工作。 这些酶 在物种上表现出了显著的遗传保守性， 印刷受体. 因此，我们从学习中获得的知识是 适用于生物化学过程中的一个有机体。 我们的最终 我们的目标是详细了解维生素的化学性质。

We propose to continue our studies of the likely reactants and products of biotin mediated carboxylation reactions. Biotin is a vitamin that serves as an obligatory cofactor for a host of carboxylase and decarboxylase enzymes. Our studies will center around the details of half reaction mechanisms currently being proposed for the uptake and transfer of biological carbon dioxide catalyzed by these enzymes. Our principal tools will be high resolution X-ray diffraction and quantum chemical techniques, and these will be employed to study the electronic, vibronic and geometrical properties of reactants and products as well as the most probable reaction pathways that interconnect them. Our goal is to perfect these techniques further and apply them to the biotin questions at large. As a by-product we expect the new approaches to be more robust, simpler to use, and suitable for wider application to biologically interesting problems. The biotin enzymes play pivotal roles in metabolism. Pyruvate carboxylase catalyzes the critical step in gluconeogenesis. Acetylcoenzyme A carboxylase plays that role in fatty acid synthesis. Other biotin dependent enzymes are involved in amino acid and purine metabolism. The preponderance of evidence is that all the biotin enzymes work with a common mechanism. These enzymes show a remarkable degree of genetic conservation, over species and substrates. Therefore, the knowledge we gain from our studies is applicable to a vide body of biochemical processes. Our ultimate goal is to understand the chemistry of the vitamin in detail.