CATs and HATs: the SLC7 family of amino acid transporters

• Published in: Pflügers Archiv 2004-02, Vol.447 (5), p.532-542
• Main Authors: Verrey, François, Closs, Ellen I, Wagner, Carsten A, Palacin, Manuel, Endou, Hitoshi, Kanai, Yoshikatsu
• Format: Article
• Language: English
• Subjects: Amino Acid Transport System y+ - chemistry; Amino Acid Transport System y+ - genetics; Amino Acid Transport System y+ - physiology; Amino acids; Amino Acids - metabolism; Animals; Biological Transport - physiology; Cations - metabolism; Cats; Humans; Multigene Family - physiology; Nitric oxide
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-003-1086-z

The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1-4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5-11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system x(c)(-)) and cationic amino acids plus neutral amino acids (system y(+)L and b(0,+)-like). Cotransport of Na(+) is observed only for the y(+)L transporters when they carry neutral amino acids. Mutations in b(0,+)-like and y(+)L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectively.