Ammonium homeostasis and human Rhesus glycoproteins

The brain ammonium production is detoxified by astrocytes, the gut ammonium production is detoxified by hepatic cells, and the renal ammonium production plays a major role in renal acid excretion. As a result of ammonium handling in these organs, the ammonium and pH values are strictly regulated in plasma. Up until recently, it was accepted that mammalian cell transmembrane ammonium transport was due to NH(4)(+) transport by non-specific transporting systems, and to non-ionic NH(3) diffusion, whereas lower organisms (such as bacteria, yeasts and plants) were endowed with specific ammonium transporters (Amts). Sequence homologies between Amts and human Rhesus (Rh) glycoproteins (RhAG, from erythroid cells, and RhBG and RhCG from epithelial cells) raised the hypothesis that Rh glycoproteins act as specific ammonium transporters, further sustained by the polarized distribution of RhBG and RhCG in gut, kidney and liver. Results from functional studies agree that Rh glycoproteins are the first ammonium transporters reported in mammals. However, the nature of the transported specie(s) is much debated: in particular, it is proposed that Rh glycoproteins mediate a direct NH(3) transport, or that they mediate an indirect NH(3) transport (resulting from NH(4)(+) for H(+) exchange). Direct NH(3) transport (associated or not with NH(4)(+) transport) raises the exciting hypothesis that Rh glycoproteins may also transport other gases than NH(3) (namely, CO(2)).