Marcolongo Paola, Fulceri Rosella, Gamberucci Alessandra, Czegle Ibolya, Banhegyi Gabor, Benedetti Angelo
Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy.
Biochim Biophys Acta. 2013 Mar;1830(3):2608-18. doi: 10.1016/j.bbagen.2012.12.013.
The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. The enzyme is a part of a multicomponent system that includes several integral membrane proteins; the catalytic subunit (G6PC) and transporters for glucose-6-phosphate, inorganic phosphate and glucose. The G6PC gene family presently includes three members, termed as G6PC, G6PC2, and G6PC3. Although the three isoforms show a moderate amino acid sequence homology, their membrane topology and catalytic site are very similar. The isoforms are expressed differently in various tissues. Mutations in all three genes have been reported to be associated with human diseases.
The present review outlines the biochemical features of the G6PC gene family products, the regulation of their expression, their role in the human pathology and the possibilities for pharmacological interventions.
G6PCs emerge as integrators of extra- and intracellular glucose homeostasis. Beside the well known key role in blood glucose homeostasis, the members of the G6PC family seem to play a role as sensors of intracellular glucose and of intraluminal glucose/glucose-6-phosphate in the endoplasmic reticulum.
Since mutations in the three G6PC genes can be linked to human pathophysiological conditions, the better understanding of their functioning in connection with genetic alterations, altered expression and tissue distribution has an eminent importance.
内质网酶葡萄糖-6-磷酸酶催化葡萄糖-6-磷酸水解为葡萄糖和无机磷酸。该酶是一个多组分系统的一部分，该系统包括几种整合膜蛋白；催化亚基（G6PC）以及葡萄糖-6-磷酸、无机磷酸和葡萄糖的转运体。G6PC基因家族目前包括三个成员，分别称为G6PC、G6PC2和G6PC3。尽管这三种同工型显示出适度的氨基酸序列同源性，但其膜拓扑结构和催化位点非常相似。这些同工型在各种组织中的表达有所不同。据报道，所有这三个基因的突变都与人类疾病有关。
本综述概述了G6PC基因家族产物的生化特征、其表达的调控、它们在人类病理学中的作用以及药物干预的可能性。
G6PCs成为细胞外和细胞内葡萄糖稳态的整合者。除了在血糖稳态中众所周知的关键作用外，G6PC家族成员似乎还作为细胞内葡萄糖以及内质网腔内葡萄糖/葡萄糖-6-磷酸的传感器发挥作用。
由于三个G6PC基因的突变可能与人类病理生理状况相关，因此更好地了解它们在基因改变、表达改变和组织分布方面的功能具有重要意义。
