Palacín Manuel, Bertran Joan, Chillarón Josep, Estévez Raúl, Zorzano Antonio
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Parc Científic de Barcelona, Avenidda Diagonal 645, Barcelona 08028, Spain.
Mol Genet Metab. 2004 Apr;81 Suppl 1:S27-37. doi: 10.1016/j.ymgme.2003.11.015.
Heteromeric amino acid transporters (HATs) are composed of two subunits, a polytopic membrane protein (the light subunit) and a disulfide-linked type II membrane glycoprotein (the heavy subunit). HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y(+)L isoforms, asc, xc-, and b(0,+)). The light subunits confer the amino acid transport specificity to the HAT. Two transporters of this family are relevant for inherited aminoacidurias. Mutations in any of the two genes coding for the subunits of system b(0,+) (rBAT and b(0,+)AT) lead to cystinuria (MIM 220100). Transport defects in a system y(+)L isoform, composed of 4F2hc and y(+)LAT-1, result in lysinuric protein intolerance (LPI) (MIM 222700). In this case, only mutations in the light subunit y(+)LAT-1, but not in the heavy chain 4F2hc, cause the disease. LPI, in addition to affecting intestinal and renal reabsorption of amino acids, is a multisystemic disease affecting the urea cycle and presents also with symptoms related to the immune system. The pathogenesis of these alterations is less well, or not understood at all.
异源氨基酸转运体（HATs）由两个亚基组成，一个是多次跨膜蛋白（轻亚基），另一个是二硫键连接的II型膜糖蛋白（重亚基）。HATs代表了几种经典的哺乳动物氨基酸转运系统（例如，L亚型、y(+)L亚型、asc、xc-和b(0,+)）。轻亚基赋予HAT氨基酸转运特异性。该家族的两种转运体与遗传性氨基酸尿症相关。编码系统b(0,+)亚基（rBAT和b(0,+)AT）的两个基因中任何一个发生突变都会导致胱氨酸尿症（MIM 220100）。由4F2hc和y(+)LAT-1组成的系统y(+)L亚型的转运缺陷会导致赖氨酸尿性蛋白不耐受症（LPI）（MIM 222700）。在这种情况下，只有轻亚基y(+)LAT-1发生突变，而重链4F2hc不发生突变才会引发疾病。LPI除了影响肠道和肾脏对氨基酸的重吸收外，还是一种影响尿素循环的多系统疾病，并且还会出现与免疫系统相关的症状。这些改变的发病机制了解较少或根本不清楚。
