Pyrimidine nucleotide monophosphate biosynthesis ends in the cytosol with uridine monophosphate (UMP). UMP phosphorylation to uridine diphosphate (UDP) by UMP KINASEs (UMKs) is required for the generation of all pyrimidine (deoxy)nucleoside triphosphates as building blocks for nucleic acids and central metabolites like UDP-glucose. The Arabidopsis (Arabidopsis thaliana) genome encodes five UMKs and three belong to the AMP KINASE (AMK)-like UMKs, which were characterized to elucidate their contribution to pyrimidine metabolism. Mitochondrial UMK2 and cytosolic UMK3 are evolutionarily conserved, whereas cytosolic UMK1 is specific to the Brassicaceae. In vitro, all UMKs can phosphorylate UMP, cytidine monophosphate (CMP) and deoxycytidine monophosphate (dCMP), but with different efficiencies. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-induced null mutants were generated for UMK1 and UMK2, but not for UMK3, since frameshift alleles were lethal for germline cells. However, a mutant with diminished UMK3 activity showing reduced growth was obtained. Metabolome analyses of germinating seeds and adult plants of single and higher-order mutants revealed that UMK3 plays an indispensable role in the biosynthesis of all pyrimidine (deoxy)nucleotides and UDP-sugars, while UMK2 is important for dCMP recycling that contributes to mitochondrial DNA stability. UMK1 is primarily involved in CMP recycling. We discuss the specific roles of these UMKs referring also to the regulation of pyrimidine nucleoside triphosphate synthesis.

中文翻译：

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三种拟南芥 UMP 激酶在嘧啶核苷酸生物合成和（脱氧）CMP 挽救中具有不同的作用


嘧啶核苷酸单磷酸生物合成在细胞质中以尿苷单磷酸 (UMP) 结束。 UMP 激酶 (UMK) 将 UMP 磷酸化为尿苷二磷酸 (UDP)，是生成所有嘧啶（脱氧）核苷三磷酸（作为核酸和中心代谢物（如 UDP-葡萄糖）的构建模块）所必需的。拟南芥 (Arabidopsis thaliana) 基因组编码 5 个 UMK，其中 3 个属于 AMP 激酶 (AMK) 样 UMK，对其进行表征以阐明它们对嘧啶代谢的贡献。线粒体 UMK2 和胞质 UMK3 在进化上是保守的，而胞质 UMK1 是十字花科特有的。在体外，所有 UMK 均可磷酸化 UMP、胞苷单磷酸 (CMP) 和脱氧胞苷单磷酸 (dCMP)，但效率不同。 UMK1 和 UMK2 产生了成簇的规则间隔短回文重复序列 (CRISPR)/CRISPR 相关核酸酶 9 (Cas9) 诱导的无效突变体，但 UMK3 则不然，因为移码等位基因对于种系细胞是致命的。然而，获得了UMK3活性降低且生长减少的突变体。对单突变体和高阶突变体的发芽种子和成年植物的代谢组分析表明，UMK3 在所有嘧啶（脱氧）核苷酸和 UDP 糖的生物合成中起着不可或缺的作用，而 UMK2 对于 dCMP 回收很重要，有助于线粒体 DNA 的稳定性。 UMK1 主要参与 CMP 回收。我们讨论了这些 UMK 的具体作用，也涉及嘧啶核苷三磷酸合成的调节。