Amino acid-sensing mechanisms: Biochemistry and behavior

Sensors are crucial components in homeostatic control systems. Amino acids (AAs) are the building blocks of protein; all 20 standard AAs that are used in protein synthesis must be available simultaneously for an organism to maintain homeostasis and survive. Therefore, a sensory system for AAs is essential for protein synthesis and survival. In living organisms, biochemical and behavioral observations demonstrate AA sensing. Taste receptors that respond to both l- and d-AAs, as well as umami taste, exist in animals and humans; they may signal high dietary protein. The gastrointestinal (GI) tract may taste ingested nutrients as well. Postabsorptively, the conserved mammalian target of rapamycin (mTOR) is activated by increases in nutrients, particularly leucine. These three: taste, gut sensors, and mTOR, may serve as adequate diet sensors. In addition, mTOR signals tissue accretion and satiety. Transporters for AAs respond to changes in substrate availability; sodium-dependent transporters can be electrogenic and activate neural feeding systems. Also conserved, the general AA control non-derepressing system (GCN) is activated by AA deprivation via uncharged tRNA, leading to AA biosynthesis in yeast or to diet rejection and increased foraging in animals. Thus, two postabsorptive systems, conserved from yeast to mammals, have recently been reported; the results suggest that there are separate biochemical systems for sensing high and low levels of AAs. These systems demonstrate conservation of AA sensory mechanisms across eukaryotic species.