Solute Carrier Transporters

The solute carrier (SLC) transporter superfamily is comprised of integral membrane proteins that mediate substrate transport across cell surface or cellular organelle, such as the golgi apparatus or synaptic vesicle membranes, by either a facilitated diffusion or an active transport mechanism. The function of SLC transporters may also be coupled to the cotransport of a counterion down its electrochemical gradient (e.g., Na+, H+, and Cl-). The members of the SLC superfamily are involved in the transport of a wide range of substrates including amino acids, peptides, sugars, vitamins, bile acids, neurotransmitters, and xeno-biotics. There are several reviews on the SLC family members identified across species that the reader is directed for more information (Saier et al., 1999; Saier, 2000; Hediger et al., 2004).

The Human Genome Organization (HUGO) Nomenclature Committee Database provides a comprehensive list of SLC transporter genes which are subdivided into 43 distinct subfamilies consisting of 319 separate isoforms (Hediger et al., 2004; see http://www.gene.ucl.ac.uk/nomenclature/). The SLC superfam-ily includes many pharmacokinetically important transporters such as proton dependent oligopeptide transporters (SLC15A family), organic cation transporters (SLC22A family), organic anion transporting polypeptides (SLC21A family), nucleoside transporters (SLC28, 29A family), and the monocarboxylate transporters (SLC16A family). While many other SLC subfamilies exist, these subfamilies are thought to significantly influence the bioavailability of their respective substrates and are relevant to the observed PK/PD profiles for many existing drugs and are increasingly being utilized for NCE screening in the drug discovery phase. The classifications and molecular characteristics of several important intestinal SLC transporters are described below.

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