Laboratory for Molecular Membrane Neuroscience, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Laboratory for Molecular Membrane Neuroscience, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Biochim Biophys Acta Gen Subj. 2017 Oct;1861(10):2507-2514. doi: 10.1016/j.bbagen.2017.06.003. Epub 2017 Jun 6.
Sterols are major cell membrane lipids, and in many organisms they are modified with glucose to generate sterylglucosides. Glucosylation dramatically changes the functional properties of sterols. The formation of sterylglucosides from sterols in plants, fungi, and bacteria uses UDP-glucose as a glucose donor. By contrast, sterylglucoside biosynthesis in mammals is catalyzed by the transglucosylation activity of glucocerebrosidases, with glucosylceramide acting as the glucose donor. Recent success in isolation and structural determination of sterylglucosides in the vertebrate central nervous system shows that transglucosylation also occurs in vivo. These analyses also revealed that sterylglucoside aglycons are composed of several cholesterol-related metabolites, including a plant-type sitosteryl.
In this review, we discuss the biological functions and metabolism of sterylglucosides. We also summarize new findings from studies on the metabolism of vertebrate sterylglucosides and review the circumstances underlying the recent discovery of sterylglucosides in vertebrate brain. Finally, we discuss the role of sterylglucosides in a variety of neurodegenerative disorders such as Gaucher disease and Parkinson's disease.
The biological significance of UDP-glucose-independent sterol glucosylation is still unknown, but it is plausible that glucosylation may provide sterols with novel biological functions. Even though sterol glucosylation is a simple reaction, it can dramatically change the physical properties of sterols.
Sterylglucosides may play roles in various physiological processes and in the pathogenesis of different diseases. Arriving at a better understanding of them at the organ and cellular level may open up new approaches to developing therapeutics for a variety of diseases. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa.
甾醇是细胞膜的主要脂质，在许多生物中，它们与葡萄糖结合生成甾基葡萄糖苷。糖基化极大地改变了甾醇的功能特性。植物、真菌和细菌中的甾醇生成甾基葡萄糖苷，使用 UDP-葡萄糖作为葡萄糖供体。相比之下，哺乳动物中的甾基葡萄糖苷生物合成由葡萄糖脑苷脂酶的转葡糖苷酶活性催化，葡萄糖脑苷脂作为葡萄糖供体。最近在脊椎动物中枢神经系统中分离和结构确定甾基葡萄糖苷的成功表明，体内也发生了转葡糖苷反应。这些分析还表明，甾基葡萄糖苷糖苷配基由几种胆固醇相关代谢物组成，包括植物型谷甾醇。
在这篇综述中，我们讨论了甾基葡萄糖苷的生物学功能和代谢。我们还总结了关于脊椎动物甾基葡萄糖苷代谢的研究的新发现，并回顾了最近在脊椎动物脑中发现甾基葡萄糖苷的情况。最后，我们讨论了甾基葡萄糖苷在各种神经退行性疾病中的作用，如戈谢病和帕金森病。
UDP-葡萄糖非依赖性甾醇糖基化的生物学意义尚不清楚，但糖基化可能为甾醇提供新的生物学功能是合理的。尽管甾醇糖基化是一个简单的反应，但它可以极大地改变甾醇的物理性质。
甾基葡萄糖苷可能在各种生理过程和不同疾病的发病机制中发挥作用。在器官和细胞水平上更好地了解它们可能为治疗各种疾病开辟新的途径。本文是由 Kenji Kadomatsu 和 Hiroshi Kitagawa 编辑的特刊“神经糖科学”的一部分。
