Porters (uniporters, symporters, antiporters). Transport systems are included in this subclass if they utilize a carrier-mediated process to catalyze uniport (a single species is transported either by facilitated diffusion or in a membrane potential-dependent process if the solute is charged), antiport (two or more species are transported in opposite directions in a tightly coupled process, not coupled to a direct form of energy other than chemiosmotic energy) and/or symport (two or more species are transported together in the same direction in a tightly coupled process, not coupled to a direct form of energy other than chemiosmotic energy) of secondary carriers (Forrest et al., 2010). Human solute carriers (SLCs) include more than 400 members that are organized into 65 families according to their physiological functions and sequence similarities. Different families of SLCs can adopt the same or different folds that determine the mechanism and reflect the evolutionary relationship between SLC families. Analysis of structural data showed 13 different folds covering 40 families and 343 members. Xie et al. 2022 found three new folds, one of which is in the choline-like transporter family (SLC44). A structural- and evolutionary-based classification system of solute carriers has appeared (Ferrada and Superti-Furga 2022).
Transport through lipids and aquaporins is entirely driven by the difference in osmotic pressure on the two sides of the membrane. Water transport in cotransporters and uniporters is different: It can be cotransported, energized by coupling to the substrate flux. In the K+/Cl- and the Na+/K+/2Cl- cotransporters (2.A.30), water is cotransported, while water transport in glucose uniporters (2.A.1.1) and Na+-coupled transporters of nutrients (2.A.21) and neurotransmitters (2.A.22) takes place by both osmosis and cotransport (Zeuthen, 2010). Mechanisms of secondary active transport have been studied by analyzing the effects of mutations and stoichiometries (Berlaga and Kolomeisky 2022).
Many transport proteins arose by internal multiplication of repeat units (Saier, 2003). This is particularly true for secondary carriers, a conclusion that has been confirmed (Hennerdal et al., 2010). Topologies of these membrane proteins represent a balance between long and short range lipid-protein interactions (Vitrac et al., 2011). An artificial intelligence (AI)-based method can predict distinct conformational states of membrane transporters and receptors (Schlessinger and Bonomi 2022).
A system of secondary carrier classification in wide use, specifically for humans and other mammalian species, is the solute carrier (SLC) system. The interconversion of the TC and SLC systems by family is as follows: