Roles for nucleotide phosphatases in sulfate assimilation and skeletal disease.
Roles for nucleotide phosphatases in sulfate assimilation and skeletal disease.
复制标题
核苷酸磷酸酶在硫酸盐同化和骨骼疾病中的作用。
DOI：
10.1016/j.advenzreg.2011.11.002
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发表时间：
2012
影响因子：
--
通讯作者：
York,JohnD
中科院分区：
文献类型：
--
作者：
Hudson,BenjaminH;York,JohnD
硫是所有生命领域的必需元素，用于重要的细胞过程，包括含硫氨基酸的合成、细胞氧化还原状态的维持以及掺入各种代谢物。无机硫酸盐是环境硫最丰富的来源，被代谢成两种常见的核苷酸前体：腺苷 5'-磷酸硫酸盐 (APS) 和 3'-磷酸腺苷 5'-磷酸硫酸盐 (PAPS)。活性硫的捐赠是通过一系列酶促反应发生的，其中许多酶促反应消耗 PAPS，从而产生 3'-磷酸腺苷 5'-磷酸 (PAP)。然后，两类 3’-核苷酸磷酸酶将 PAP 水解成 5’-AMP：一类在从细菌到人类的进化过程中是保守的，定位于细胞质区室，而另一类仅限于真核生物的子集，在高尔基体腔内活跃。有趣的是，这两类 3'-核苷酸酶都是结构保守的锂抑制磷酸酶家族的成员，这些磷酸酶是多种生物体中药物的靶标。在这篇综述中，我们概述了硫同化以及 3’-核苷酸酶在从耐盐性到糖胺聚糖硫酸化等过程中发挥的广泛调节作用。此外，我们还讨论了最近的植物和动物研究，这些研究强调了 3’-核苷酸酶功能在发育生物学、生理学以及罕见的骨骼异常人类患者中的作用。
Sulfur is an essential element to all kingdoms of life and is used in essential cellular processes including the synthesis of sulfur-containing amino acids, maintenance of cellular redox states, and incorporation into various metabolites. Inorganic sulfate, the most abundant source of environmental sulfur, is metabolized into two commonly formed nucleotide precursors: adenosine 5’-phosphosulfate (APS) and 3’-phosphoadenosine 5’-phosphosulfate (PAPS). Donation of activated sulfur occurs through a broad range of enzymatic reactions many of which consume PAPS thereby producing 3’-phosphoadenosine 5’-phosphate (PAP). Two classes of 3’-nucleotide phosphatases then hydrolyze PAP into 5’-AMP: one is evolutionarily conserved from bacteria to man and localizes to the cytoplasmic compartment, while the other is restricted to a subset of eukaryotes and is active within the Golgi lumen. Interestingly, both classes of 3’-nucleotidase are members of a structurally conserved family of lithium-inhibited phosphatases that are targets of the drug in a variety of organisms. In this review we provide an overview of sulfur assimilation and the broad regulatory roles that 3’-nucleotidases play in processes ranging from halotolerance to glycosaminoglycan sulfation. In addition, we discuss recent plant and animal studies that emphasize roles for 3’-nucleotidase function in developmental biology, physiology, and in a rare subset of human patients with skeletal abnormalities.