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Pyrimidine biosynthesis

Reactome ID: R-HSA-500753

中文名称

嘧啶生物合成

通路描述

嘧啶或尿嘧啶(尿嘧啶酸)是在四步反应中合成的,其原子来自谷氨酰胺、碳酸氢盐和天冬氨酸。一个多功能胞质酶催化前三个反应,而最后一个反应由与内质网膜相关的酶催化。在另外两个反应中,由双功能胞质酶催化,尿嘧啶与1-磷酸核糖基5-焦磷酸(PRPP)反应生成尿苷5'-单磷酸,然后脱羧生成尿苷5'-单磷酸(UMP)。虽然此途径中的几个单独反应是可逆的,但其他不可逆反应驱动途径向UMP生物合成方向进行。因此,这里仅在此处注释正向反应。该途径在仓鼠细胞系中已最广泛分析。所有三种酶也已从人类来源纯化,并且这些反应的关键特征已从该人类材料的研究中得到确认(Jones 1980; Webster et al. 2001)。所有其他嘧啶都是从UMP合成的。这里注释的反应,由dCMP脱氨酶和dUTP二磷酸酶催化,生成dUMP,后者随后由胸苷酸合成酶转化为TMP。
英文描述
Pyrimidine biosynthesis The pyrimidine orotate (orotic acid) is synthesized in a sequence of four reactions, deriving its atoms from glutamine, bicarbonate, and aspartate. A single multifunctional cytosolic enzyme catalyzes the first three of these reactions, while the last one is catalyzed by an enzyme associated with the inner mitochondrial membrane. In two further reactions, catalyzed by a bifunctional cytosolic enzyme, orotate reacts with 1-phosphoribosyl 5-pyrophosphate (PRPP) to yield orotidine 5'-monophosphate, which is decarboxylated to yield uridine 5'-monophosphate (UMP). While several individual reactions in this pathway are reversible, other irreversible reactions drive the pathway in the direction of UMP biosynthesis in the normal cell. All reactions are thus annotated here only in the forward direction.This pathway has been most extensively analyzed at the genetic and biochemical level in hamster cell lines. All three enzymes have also been purified from human sources, however, and the key features of these reactions have been confirmed from studies of this human material (Jones 1980; Webster et al. 2001).All other pyrimidines are synthesized from UMP. The reactions annotaed here, catalyzed by dCMP deaminase and dUTP diphosphatase yield dUMP, which in turn is converted to TMP by thymidylate synthase.

所含基因

3 个基因