Jakobsson Eric, Argüello-Miranda Orlando, Chiu See-Wing, Fazal Zeeshan, Kruczek James, Nunez-Corrales Santiago, Pandit Sagar, Pritchet Laura
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
J Membr Biol. 2017 Dec;250(6):587-604. doi: 10.1007/s00232-017-9998-2. Epub 2017 Nov 10.
Lithium has literally been everywhere forever, since it is one of the three elements created in the Big Bang. Lithium concentration in rocks, soil, and fresh water is highly variable from place to place, and has varied widely in specific regions over evolutionary and geologic time. The biological effects of lithium are many and varied. Based on experiments in which animals are deprived of lithium, lithium is an essential nutrient. At the other extreme, at lithium ingestion sufficient to raise blood concentration significantly over 1 mM/, lithium is acutely toxic. There is no consensus regarding optimum levels of lithium intake for populations or individuals-with the single exception that lithium is a generally accepted first-line therapy for bipolar disorder, and specific dosage guidelines for sufferers of that condition are generally agreed on. Epidemiological evidence correlating various markers of social dysfunction and disease vs. lithium level in drinking water suggest benefits of moderately elevated lithium compared to average levels of lithium intake. In contrast to other biologically significant ions, lithium is unusual in not having its concentration in fluids of multicellular animals closely regulated. For hydrogen ions, sodium ions, potassium ions, calcium ions, chloride ions, and magnesium ions, blood and extracellular fluid concentrations are closely and necessarily regulated by systems of highly selective channels, and primary and secondary active transporters. Lithium, while having strong biological activity, is tolerated over body fluid concentrations ranging over many orders of magnitude. The lack of biological regulation of lithium appears due to lack of lithium-specific binding sites and selectivity filters. Rather lithium exerts its myriad physiological and biochemical effects by competing for macromolecular sites that are relatively specific for other cations, most especially for sodium and magnesium. This review will consider what is known about the nature of this competition and suggest using and extending this knowledge towards the goal of a unified understanding of lithium in biology and the application of that understanding in medicine and nutrition.
锂实际上一直无处不在，因为它是宇宙大爆炸时产生的三种元素之一。岩石、土壤和淡水中的锂浓度在各地差异很大，并且在特定区域的演化和地质时期内也有很大变化。锂的生物学效应多种多样。基于动物被剥夺锂的实验，锂是一种必需营养素。另一方面，当锂摄入量足以使血液浓度显著超过1毫摩尔/升时，锂具有急性毒性。对于人群或个体的最佳锂摄入量水平尚无共识——唯一的例外是锂是双相情感障碍普遍接受的一线治疗药物，并且该疾病患者的具体剂量指南已基本达成共识。将社会功能障碍和疾病的各种标志物与饮用水中锂水平相关联的流行病学证据表明，与平均锂摄入量相比，适度提高锂水平有益处。与其他具有生物学意义的离子不同，锂的不同寻常之处在于其在多细胞动物体液中的浓度没有受到严格调节。对于氢离子、钠离子、钾离子、钙离子、氯离子和镁离子，血液和细胞外液浓度由高度选择性的通道系统以及初级和次级主动转运体进行严格且必要的调节。锂虽然具有很强的生物活性，但在跨越多个数量级的体液浓度范围内都能被耐受。锂缺乏生物学调节似乎是由于缺乏锂特异性结合位点和选择性过滤器。相反，锂通过竞争对其他阳离子相对特异的大分子位点发挥其众多的生理和生化作用，尤其是对钠和镁。本综述将考虑关于这种竞争性质的已知信息，并建议利用和扩展这些知识，以实现对锂在生物学中的统一理解，并将这种理解应用于医学和营养领域。
