Abstract:
Discovered in 1993, inositol pyrophosphates are evolutionarily conserved signaling metabolites whose versatile modes of action are being increasingly appreciated. These include their emerging roles as energy regulators, phosphodonors, steric/allosteric regulators, and G protein-coupled receptor messengers. Through studying enzymes that metabolize inositol pyrophosphates, progress has also been made in elucidating the various cellular and physiological functions of these pyrophosphate-containing, energetic molecules. The two main forms of inositol pyrophosphates, 5-IP7 and IP8, synthesized respectively by inositol-hexakisphosphate kinases (IP6Ks) and diphosphoinositol pentakisphosphate kinases (PPIP5Ks), regulate phosphate homeostasis, ATP synthesis, and several other metabolic processes ranging from insulin secretion to cellular energy utilization. Here, we review the current understanding of the catalytic and regulatory mechanisms of IP6Ks and PPIP5Ks, as well as their counteracting phosphatases. We also highlight the genetic and cellular evidence implicating inositol pyrophosphates as essential mediators of mammalian metabolic homeostasis.
摘要:
1993年发现的肌醇焦磷酸是进化上保守的信号代谢产物,其通用的作用方式日益受到重视。这些包括他们作为能源监管机构的新兴角色,磷酸供体,空间/变构调节剂,和G蛋白偶联受体信使。通过研究代谢肌醇焦磷酸盐的酶,在阐明这些含有焦磷酸盐的各种细胞和生理功能方面也取得了进展,高能分子.肌醇焦磷酸盐的两种主要形式,5-IP7和IP8,分别由肌醇六磷酸激酶(IP6Ks)和二磷酸肌醇五磷酸激酶(PPIP5Ks)合成,调节磷酸盐稳态,ATP合成,以及从胰岛素分泌到细胞能量利用的其他几种代谢过程。这里,我们回顾了目前对IP6Ks和PPIP5Ks的催化和调节机制的理解,以及它们的抵消磷酸酶。我们还强调了遗传和细胞证据,表明肌醇焦磷酸是哺乳动物代谢稳态的必需介质。