Molecular Ontology of Amino Acid Transport

Abstract

This review focuses on the comparative physiology and phylogeny of plasma membrane transporters that absorb and redistribute amino acids in organisms. The first section briefly summarizes the life history of the environmental flux and metabolism of amino acids. It reveals a set of geological and biological events that may have shaped amino acid transport mechanisms, which evolved under everlasting antagonism of environmental availability, endogenous synthesis, and metabolic consumption of proteinogenic amino acids. The second section addresses the phylogenetic and physiological diversity of experimentally and theoretically defined amino acid transporters. It reveals a set of gene duplications, expansions, and extinctions in the phylogenetic tree of the amino acid transporters, which correlate with the rapid acquisitions of new transport phenotypes and assured remarkable adaptive plasticity of the amino acid transport network. Specific emphasis in this review is placed on the Excitatory Amino Acid Transporters and the Sodium Neurotransmitter symporter families (SLC1 and SLC6, respectively). The early evolution of these cation-coupled transporters compensating the anabolism of proteinogenic amino acids may have simultaneously driven the expansion of heterotrophy and the extinction of principal metabolic pathways (e.g. nitrogen fixation in prokaryotes and essential amino acid synthesis cascades in Metazoans). Furthermore, the extant physiological functions of these transporters – including the balance of dispensable and essential amino acids, cellular signaling, and neurochemical communication – are critical for the metabolic integrity and health of metazoan organisms. Molecular, genetic, and structural analyses of amino acid transporters have emphasized this point, and continue to provide us with an expanding knowledge base that will ultimately lead to new biomedical technologies for curing metabolic disorders and controlling pathogenic and pest organisms.