Letter to the editor: "The origin of free glutamate in milk: a role for anionic amino acid transporters".

TO THE EDITOR: Matsumoto et al. (3) have reported that the lactating rat mammary gland maintains a large transepithelial L-glutamate concentration gradient in favor of milk and provide a model for the production of free L-glutamate in milk. They suggest that L-leucine is the major source of milk L-glutamate; it is envisaged that L-leucine is transported across the basolateral membrane of mammary secretory cells via LAT1 (SLC7A5) and a moiety is then subsequently transaminated intracellularly by branched-chain aminotransferase. While Matsumoto et al. (3) provide evidence that L-leucine could possibly be a source of milk L-glutamate they do not provide any insight into the mechanism of L-glutamate transport across the apical membrane of mammary secretory cells. More importantly, however, their model appears to rule out plasma L-glutamate as an important source of milk L-glutamate despite an abundance of evidence for the uptake of anionic amino acids by the lactating rat mammary gland. First, the lactating rat mammary gland is capable of generating a substantial arteriovenous L-glutamate concentration gradient that can be reduced by starvation and milk stasis, suggesting that the uptake of L-glutamate uptake by secretory cells is a highly regulated process (7, 8). Second, the lactating rat mammary gland transports anionic amino acids via a high-affinity, Na -dependent mechanism whose characteristics resemble system X AG (4, 5). It is apparent that system X AG is the predominant, if not sole, pathway for the transport of L-glutamate by rat mammary tissue. Evidence from experiments employing a rapid, paired-tracer dilution technique to measure anionic amino acid transport by the perfused lactating rat mammary gland (4, 5) suggests that system X AG is located in the basolateral membrane and is thus in a position to play a role in establishing the large intracellular L-glutamate pool in rat mammary tissue (6). Third, mRNA for several molecular correlates of system X AG, namely SLC1A1, SLC1A2, and SLC1A3, are expressed in rat mammary tissue although the exact contribution of each of the transporters to L-glutamate transport remains to be established (1, 2). It is evident that any model describing the origin of L-glutamate in milk (either free or protein bound) needs to incorporate the transport of L-glutamate across the basolateral membrane of secretory cells. The relative contribution of L-glutamate transport and transamination of branched-chain amino acids to the intracellular L-glutamate pool remains to be established as does the mechanism of L-glutamate efflux across the apical pole of the mammary epithelium.