FIGURE 8.

Cartoon illustrating the proposed mechanism of lactic acid transport by MCT1. Lactic acid protonates Lys³⁸ (K) causing the channel to open. Lactate then moves into the open extracellular side of the pore and forms an ion pair with Lys³⁸. In the next step the proton on Lys³⁸ is transferred to aspartate 302 (D-) neutralizing the aspartate side chain (DH). This is followed by migration of lactate through the pore where it forms an ion pair with R306 (R+). The size of the adjacent side chain of residue 360 (F) governs the ability of this site to bind the α-hydroxy acid. Once Lys³⁸ is deprotonated, and lactate is occupying the specificity filter, the transporter relaxes back toward the closed state and releases lactic acid into the intracellular space.