The absorption of zwitterionic imino and
amino acids, and related drugs, is an essential function of the small intestinal epithelium. This review focuses on the physiological roles of transporters recently identified at the molecular level, in particular SLC36A1, by identifying how they relate to the classical epithelial imino and
amino acid transporters characterised in mammalian small intestine in the 1960s-1990s. SLC36A1 transports a number of D- and L-imino and
amino acids, beta- and gamma-
amino acids and orally-active neuromodulatory and
antibacterial agents. SLC36A1 (or PAT1) functions as a
proton-coupled imino and
amino acid symporter in cooperation with the Na+/H+ exchanger NHE3 (SLC9A3) to produce the imino
acid carrier identified in rat small intestine in the 1960s but subsequently ignored because of
confusion with the IMINO transporter. However, it is the
sodium/imino and
amino acid cotransporter SLC6A20 which corresponds to the
betaine carrier (identified in hamster, 1960s) and IMINO transporter (identified in rabbit and guinea pig, 1980s). This review summarises evidence for expression of SLC36A1 and SLC6A20 in human small intestine, highlights the differences in functional characteristics of the imino
acid carrier and IMINO transporter, and explains the
confusion surrounding these two distinct transport systems.