BIOSYNTHESIS OF VITAMIN B1 AND VITAMIN B6

值得注意的是，在发现和合成了60年后 维生素B1和维生素B6及其营养价值的认识 重要性，以及在阐明它们的生物化学30年后 功能，但关于它们的生物合成的知识仍然不完整。少校 这两种维生素的碳源都是葡萄糖。路线 对于细菌中的两种维生素，大肠杆菌，正在变得清晰， 但问题依然存在。另一条尚未定义的通向B1的路线正在运行 放在酵母里。在酵母中通向B6的途径尚不清楚。 本提案的两个主要目标是：(一)澄清 在酵母中导致这两种维生素的步骤，以及关键的 关于是否存在前体产品问题的考察 这两种维生素之间的关系；以及(Ii)最后澄清 两种代谢途径中几种中间体的研究现状 大肠杆菌中的维生素。 维生素B1：倍增13C标记样品的掺入研究 葡萄糖和核糖将定义C1和C2单元的进入模式， 两者都源于核糖，在大肠杆菌中进入B1中的嘧啶部分，以及 将确定葡萄糖衍生的碳原子的确切来源 酵母中的硫胺素。大多数所需的倍增13C标记样本将 必须合成，因为它们不能在商业上买到。 维生素B6：酵母中B6的来源尚不清楚。不能假设它是 在酵母中通向B6的途径与在大肠杆菌中相同， 由于其他维生素(如硫胺素、烟酸)有不同的来源模式 在原核生物和真核生物中。将回答两个问题：模式是 在酵母中B6的生物合成与在大肠杆菌中的相同或不同。 (Ii)酵母中的维生素B6是维生素的嘧啶单位的前体 B1，正如最近提出的那样。13C标记倍增的实验研究 底物，然后用高场13C核磁共振进行分析，将提供 将有助于回答这些问题的证据。 根据定义，维生素不是在哺乳动物中合成的。现在很明显了 B1和B6的主要前体是葡萄糖和其他常见的 代谢物。这项研究的长远目标是找出 在人体组织中被阻断的每一条途径中的每一步，从而使 复合维生素。

It is remarkable that 60 years after the discovery and synthesis of Vitamin B1 and of Vitamin B6, and the recognition of their nutritional importance, and 30 years after the elucidation of their biochemical function, knowledge of their biosynthesis is still incomplete. The major source of the carbons of each of the two Vitamins is glucose. The routes to the two Vitamins in a bacterium, Escherichia coli, are becoming clear, but questions remain. A different, as yet undefined, route to B1 operates in yeast. The path to B6 in yeast is unknown. The two major objectives of the present proposal are (i) the elucidation of the steps leading to the two Vitamins in yeast, and a critical examination of the question whether there exists a precursor-product relationship between the two Vitamins; and (ii) final clarification of the status of several intermediates of the metabolic routes to the two Vitamins in E.coli. Vitamin B1: Incorporation studies with multiply 13C labeled samples of glucose and ribose will define the mode of entry of a C1 and a C2 unit, both derived from ribose, into the pyrimidine moiety in B1 in E. coli, and will determine the precise origin of the glucose-derived carbon atoms of thiamin in yeast. Most of the required multiply 13C labeled samples will have to be synthesized since they are not available commercially. Vitamin B6: The origin of B6 in yeasts is unknown. It cannot be assumed a priori that the route to B6 in yeast is identical with that in E.coli, since other Vitamins (e.g., thiamin, niacin) have distinct modes of origin in prokaryotes and eukaryotes. Two questions will be answered: Is the mode of biosynthesis of B6 in yeast the same or different from that in E. coli. (ii) In yeast is Vitamin B6 a precursor of the pyrimidine unit of Vitamin B1, as has recently been suggested. Experiments with multiply 13 C-labeled substrates, followed by analysis by high field 13C NMR, will provide the evidence which will serve to answer these questions. By definition, Vitamins are not synthesized in mammals. It is now evident that the primary precursor of B1 and B6 are glucose and other common metabolites. It is the long term objective of the study to identify the step in each pathway which is blocked in human tissues, thereby making the compounds Vitamins.