Lagarde M
U 585 INSERM/INSA-Lyon, Bâtiment Louis Pasteur, 20, avenue Albert-Einstein, 69621 Villeurbanne, France.
Pathol Biol (Paris). 2003 Jul;51(5):241-3. doi: 10.1016/s0369-8114(03)00076-2.
In addition to their well-known roles as structural elements (amphiphilic lipids of the cell membranes) and as energetic reserve (essentially triglycerides), the lipids function as "second messengers" is increasingly recognised. Indeed, they are also endogenous mediators with specific biological activities, synthesized "on request", often in response to a primary cellular signal. Most of the bio-active lipids originate from cleavage of the membrane structures under the action of phospholipases A2, C, D and of sphigomyelinases. Several products of lipolysis are involved in cell activation, signalling, apoptosis or proliferation. One of the major cascades of bio-active lipid production involves the release of arachidonic acid followed by the formation of prostanoids, e.g.: prostaglandins, thromboxanes, and of leukotrienes and related products. These molecules play major roles in such biological processes as inflammation or thrombosis. Arachidonic acid is also the substrate for cytochrome P450-dependent mono-oxygenases, producing molecules regulating ion fluxes in cell membranes. Action of sphingomyelinases leads to the release of ceramides, associated with apoptosis. Further hydrolysis of ceramides produces fatty acids and sphingosine; the latter being able, in its phosphorylated form, to induce cell proliferation and re-equilibrate the balance between cell death and cell renewal.
除了作为结构成分(细胞膜的两亲性脂质)和能量储备(主要是甘油三酯)这些广为人知的作用外,脂质作为“第二信使”的功能也越来越受到认可。事实上,它们还是具有特定生物活性的内源性介质,通常根据细胞的初始信号“按需”合成。大多数生物活性脂质源自磷脂酶A2、C、D以及鞘磷脂酶作用下膜结构的裂解。脂肪分解的几种产物参与细胞活化、信号传导、细胞凋亡或增殖过程。生物活性脂质产生的主要级联反应之一涉及花生四烯酸的释放,随后生成前列腺素类物质,例如:前列腺素、血栓素,以及白三烯和相关产物。这些分子在炎症或血栓形成等生物过程中发挥着重要作用。花生四烯酸也是细胞色素P450依赖性单加氧酶的底物,可生成调节细胞膜离子通量的分子。鞘磷脂酶的作用导致神经酰胺的释放,这与细胞凋亡有关。神经酰胺的进一步水解产生脂肪酸和鞘氨醇;后者以其磷酸化形式能够诱导细胞增殖并重新平衡细胞死亡和细胞更新之间的平衡。