Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria.
Biophys J. 2010 Jul 21;99(2):499-506. doi: 10.1016/j.bpj.2010.04.028.
Sphingolipid signaling plays an important, yet not fully understood, role in diverse aspects of cellular life. Sphingomyelinase is a major enzyme in these signaling pathways, catalyzing hydrolysis of sphingomyelin to ceramide and phosphocholine. To address the related membrane dynamical structural changes and their feedback to enzyme activity, we have studied the effect of enzymatically generated ceramide in situ on the properties of a well-defined lipid model system. We found a gel-phase formation that was about four times faster than ceramide generation due to ceramide-sphingomyelin pairing. The gel-phase formation slowed down when the ceramide molar ratios exceeded those of sphingomyelin and stopped just at the solubility limit of ceramide, due to unfavorable pairwise interactions of ceramide with itself and with monounsaturated phosphatidylcholine. A remarkable correlation to in vitro experiments suggests a regulation of sphingomyelinase activity based on the sphingomyelin/ceramide molar ratio.
鞘脂信号在细胞生命的各个方面发挥着重要但尚未完全理解的作用。鞘磷脂酶是这些信号通路中的主要酶,催化鞘磷脂水解为神经酰胺和磷酸胆碱。为了解决相关的膜动力学结构变化及其对酶活性的反馈,我们研究了酶促生成的神经酰胺在原位对明确定义的脂质模型系统性质的影响。我们发现由于神经酰胺-鞘磷脂配对,凝胶相的形成速度比神经酰胺的生成速度快约四倍。当神经酰胺的摩尔比超过鞘磷脂的摩尔比时,凝胶相的形成速度会减慢,并且由于神经酰胺与自身和单不饱和磷脂酰胆碱的不利成对相互作用,凝胶相的形成会停止在神经酰胺的溶解度极限处。与体外实验的显著相关性表明,基于鞘磷脂/神经酰胺摩尔比的鞘磷脂酶活性的调节。