Michel Vera, Yuan Zongfei, Ramsubir Shobha, Bakovic Marica
Department of Human Health and Nutritional Sciences, Animal Science and Nutrition Building, Rm. 346, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Exp Biol Med (Maywood). 2006 May;231(5):490-504. doi: 10.1177/153537020623100503.
Choline is an essential nutrient for all cells because it plays a role in the synthesis of the membrane phospholipid components of the cell membranes, as a methyl-group donor in methionine metabolism as well as in the synthesis of the neurotransmitter acetylcholine. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it has been associated with liver dysfunction and cancer. Abnormal choline transport and metabolism have been implicated in a number of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therefore, the study of choline transport and the characteristics of choline transporters are of central importance to understanding the mechanisms that underlie membrane integrity and cell signaling in such disorders. Kinetic studies with radiolabeled choline and inhibitors distinguish three systems for choline transport: (i) low-affinity facilitated diffusion, (ii) high-affinity, Na+-dependent transport, and (iii) intermediate-affinity, Na+-independent transport. It is only recently, however, that the proteins having transport characteristics of at least one of these systems have been identified. They include (i) polyspecific organic cation transporters (OCTs) with low affinity for choline, (ii) high-affinity choline transporters (CHT1s), and (iii) intermediate-affinity choline transporter-like (CTL1) proteins. CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 and essentially display characteristics of specialized transporters for targeted choline metabolism. CHT1 is abundant in neurons and almost exclusively supplies choline for acetyl-choline synthesis. The focus here is more on newly-discovered CTL1 choline transporters. They are expressed in different organisms and cell types, apparently not for the biosynthesis of acetylcholine but for the production of the most abundant metabolite of choline, the membrane lipid phosphatidylcholine.
胆碱是所有细胞必需的营养素，因为它在细胞膜的膜磷脂成分合成中发挥作用，作为蛋氨酸代谢中的甲基供体以及神经递质乙酰胆碱的合成中发挥作用。胆碱缺乏会影响参与细胞增殖、分化和凋亡的基因表达，并与肝功能障碍和癌症有关。胆碱转运和代谢异常与许多神经退行性疾病有关，如阿尔茨海默病和帕金森病。因此，研究胆碱转运和胆碱转运体的特性对于理解这些疾病中膜完整性和细胞信号传导的潜在机制至关重要。用放射性标记的胆碱和抑制剂进行的动力学研究区分了三种胆碱转运系统：（i）低亲和力易化扩散，（ii）高亲和力、钠依赖性转运，以及（iii）中等亲和力、钠非依赖性转运。然而，直到最近，才鉴定出具有这些系统中至少一种转运特性的蛋白质。它们包括（i）对胆碱亲和力低的多特异性有机阳离子转运体（OCTs），（ii）高亲和力胆碱转运体（CHT1s），以及（iii）中等亲和力胆碱转运体样（CTL1）蛋白。CHT1和CTL1而非OCT转运体被半胱氨酸-3选择性抑制，并且基本上显示出针对胆碱代谢的特异性转运体的特性。CHT1在神经元中丰富，几乎专门为乙酰胆碱合成提供胆碱。这里的重点更多地放在新发现的CTL1胆碱转运体上。它们在不同的生物体和细胞类型中表达，显然不是用于乙酰胆碱的生物合成，而是用于胆碱最丰富的代谢产物——膜脂磷脂酰胆碱的产生。
