An important evidence of the crucial role of LAT1 in cell metabolism and growth derives from the lethal phenotype of knockout animal embryo, which cannot go beyond the mid-gestation stage E The identification of histidine as LAT1 high affinity substrate in vitro, lays the groundwork for interpreting following important advances in human health see section Regulation of LAT1 Expression.
Facilitated diffusion is the passage of molecules or ions across a biological membrane through specific transport proteins and requires no energy input. LAT1 is expressed in brain, ovary, testis, placenta, spleen, colon, blood-brain barrier, fetal liver, activated lymphocytes, skeletal muscle, heart, lung, thymus, and kidney Kanai et al.
The collected data suggested that the internal and external substrates are translocated in a single transport cycle, implying the simultaneous exposure of binding sites for external and internal substrates Napolitano et al. Besides glucose, glutamine represents a primary nutrient for maintenance of body's homeostasis Bode, ; Newsholme et al.
This two-faced feature elected LAT1 as a crossroad point in cell life. Each protomer is an independent transport unit and is formed by eight transmembrane domains and two hairpin loops HP1 and HP2 which are thought to be responsible of substrate translocation, being the mobile part of the transporter Boudker et al.
This is linked to the function of LAT1 in acinar cells that allows accumulation of amino acids necessary to synthesize digestive enzymes Rooman et al.
The homology structural models of rat gray and human blue B0AT1 were constructed as described in Figure 4 using as template the structure of dopamine transporter from D.
Therefore, additional constraints are needed for coupling substrate transport in opposed directions. Molecular evolution studies show that the heterodimeric amino acid transporters and the cationic amino acid transporters have a common ancestor characterized by 12 trans-membrane domains.
Two transcripts are reported in the data bases, but only one bp codes for a protein, while the other one bp undergoes nonsense mediated decay Table 1.
The eminent position assumed by LAT1 is somewhat in contrast with the scarce depth of knowledge so far achieved.