Mammals feed off yeast pathway

"What's most striking to me, because I'm a yeast geneticist, is that you'd be able to see this effect on feeding behavior," Alan Hinnebusch of the National Institutes of Health, who was not involved in the study, told The Scientist.In yeast, a deficiency of a particular amino acid causes an accumulation of that amino acid's corresponding transfer RNA. This free tRNA—called "uncharged" because it is not attached to an amino acid—activates the kinase GC nonderepressing 2 (GCN2), which then phosphorylates eukaryotic initiation factor 2 alpha (eIF-2alpha). This signal decreases the yeast's global protein synthesis and increases transcription of genes that synthesize deficient amino acids.Gietzen, postdoc Shuzhen Hao, and their colleagues wanted to see if uncharged tRNA was responsible for the rat behavior that seems like a sort of behavioral homolog of this pathway. Rats will normally spend 30-45 minutes eating, if they haven't eaten for a while before that. Beginning at about 20 minutes, researchers have shown that rats eating food deficient in essential amino acids will eat less than those eating normal food, Gietzen explained.The team directly inhibited tRNA charging in rats by injecting amino alcohols—alcohol derivatives of amino acids—into the anterior piriform cortex, a brain region that projects to feeding circuits and has long been known to sense amino acid deficiencies. Amino alcohols are selective, potent inhibitors of the synthetases that join amino acids with their respective tRNAs, Gietzen said.About 20 minutes after receiving injections of the amino alcohol L-threoninol, the rats began to eat less food than normal, as if they were eating food with no threonine, Gietzen said. After injections of L-leucinol, they also ate less than control rats.Injections of alcohol derivatives of the dispensable amino acids serine and proline, however, did not affect the rats' feeding. Also, the stereoisomer D-threoninol did not change their food intake, presumably because