Palacín M, Estévez R, Bertran J, Zorzano A
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.
Physiol Rev. 1998 Oct;78(4):969-1054. doi: 10.1152/physrev.1998.78.4.969.
Molecular biology entered the field of mammalian amino acid transporters in 1990-1991 with the cloning of the first GABA and cationic amino acid transporters. Since then, cDNA have been isolated for more than 20 mammalian amino acid transporters. All of them belong to four protein families. Here we describe the tissue expression, transport characteristics, structure-function relationship, and the putative physiological roles of these transporters. Wherever possible, the ascription of these transporters to known amino acid transport systems is suggested. Significant contributions have been made to the molecular biology of amino acid transport in mammals in the last 3 years, such as the construction of knockouts for the CAT-1 cationic amino acid transporter and the EAAT2 and EAAT3 glutamate transporters, as well as a growing number of studies aimed to elucidate the structure-function relationship of the amino acid transporter. In addition, the first gene (rBAT) responsible for an inherited disease of amino acid transport (cystinuria) has been identified. Identifying the molecular structure of amino acid transport systems of high physiological relevance (e.g., system A, L, N, and x(c)- and of the genes responsible for other aminoacidurias as well as revealing the key molecular mechanisms of the amino acid transporters are the main challenges of the future in this field.
1990 - 1991年，随着首个γ-氨基丁酸（GABA）和阳离子氨基酸转运体的克隆，分子生物学进入了哺乳动物氨基酸转运体领域。从那时起，已分离出20多种哺乳动物氨基酸转运体的cDNA。它们都属于四个蛋白质家族。在此，我们描述这些转运体的组织表达、转运特性、结构 - 功能关系以及假定的生理作用。只要有可能，我们还会提出这些转运体与已知氨基酸转运系统的归属关系。在过去3年里，哺乳动物氨基酸转运的分子生物学取得了重大进展，比如构建了阳离子氨基酸转运体CAT - 1、谷氨酸转运体EAAT2和EAAT3的基因敲除模型，以及越来越多旨在阐明氨基酸转运体结构 - 功能关系的研究。此外，已鉴定出首个与氨基酸转运遗传性疾病（胱氨酸尿症）相关的基因（rBAT）。确定具有高度生理相关性的氨基酸转运系统（如A、L、N和x(c)-系统）的分子结构以及与其他氨基酸尿症相关的基因，并揭示氨基酸转运体的关键分子机制，是该领域未来的主要挑战。
