In mammalian cells, amino acids are transported through biological membranes by various transport systems,
6 7 8 with different carrier proteins that exhibit distinct transport properties participating in the amino acid transport. Cationic amino acids (CAAs), such as lysine, arginine, and histidine, are transported through the cellular membrane by four distinct transport systems: y
+, y
+L, b
0,+, and B
0,+.
9 System y
+ includes CAA transporter (CAT)-1, -2A/2B, -3, and -4, which are found ubiquitously and transport CAAs specifically. System y
+ is pH-independent and mediates the bidirectional transport of CAAs.
10 11 12 13 System y
+L, which includes y
+LAT1 and y
+LAT2, is an exchangeable transporter that recognizes CAAs in the absence of sodium, though it requires the cation to interact with neutral amino acids (NAAs).
14 15 System b
0,+ recognizes CAAs and NAAs with a similar affinity, and transports amino acids independent of sodium,
16 whereas system B
0,+ represents an Na
+/Cl
−-dependent transport system and transports CAAs and NAAs, with the highest affinity for hydrophobic amino acids.
9 17 Although the substrate specificity of systems b
0,+ and B
0,+ is similar, the latter also accepts alanine and serine. The transport of large NAAs with branched or aromatic side chains, such as leucine, isoleucine, valine, phenylalanine, tyrosine, and tryptophan, is mediated by system L, which is Na
+-independent and a major route of branched or aromatic amino acids.
18 19 The amino acid transporter systems y
+L, system L, cystine/glutamate transporter x
− c, small neutral transporter asc, and b
0,+ require interaction via a disulfide bridge with the type II membrane glycoprotein members—namely, the heavy chains—for trafficking the transporters to the cell membrane.
20 System y
+L, system L, x
− c, and asc require 4F2hc, whereas system b
0,+ requires rBAT.