Figure 6. Scheme of the different arginine pools for nNOS in A673 and TGW-nu-I neuronal cells.

The scheme depicts different arginine pools in neuronal cells: The exchangeable pool I (red) consists of plasma membrane transporters that take up arginine from the extracellular space (CATs, for cationic amino acid transporter), but can also extract arginine from cells in exchange against other cationic (CATs and y+LATs) or neutral amino acids (y+LATs). Pool IIA (purple) is made up of the so-called recycling enzymes argininosuccinate synthase and lyase that convert citrulline to arginine. This pool is only available to nNOS in TGW-nu-I cells supplemented with extracellular citrulline. A673 cells can neither use endogenous nor exogenous citrulline as source for nNOS substrate. Pool IIB (orange) is present in both cell types. It comprises proteasomal and lysosomal protein degradation. Free arginine or arginine-containing peptides generated by the latter exit the lysosome, respectively, by the newly discovered amino acid transporter PQLC2 and peptide transporters yet to be identified. Also, the peptidase(s) that sets arginine free from peptides have not been specified to date. Peptides may also enter (or exit) neuronal cells by peptide transporters of the plasma membrane, with PHT1 exhibiting the most pronounced expression in both, A673 and TGW-nu-I cells. Pool IIB also generates the NOS inhibitor asymmetric dimethyl arginine (ADMA).