Adaptation of plasma membrane amino acid transport mechanisms to physiological demands.

The molecular identification of almost all physiologically characterized amino acid transporters in recent years has facilitated the functional analysis of this important class of transport proteins. The picture that emerges from these studies is that antiport is the prevalent mode of amino acid transport rather than a combination of uniporters and cotransporters. Mainly neurotransmitters and osmolytes are transported by complex cotransport mechanisms that allow a high intracellular accumulation. Antiport mechanisms almost invariably include the nonessential amino acids alanine and glutamine, which are used as exchange substrates. The intracellular level of both amino acids is well regulated by Na(+)/amino acid cotransporters. Transport mechanisms are not conserved within families and may change with mutation of even a single amino acid residue in the transport protein. Thus transport mechanisms are easily adapted to physiological demands during evolution.