The intracellular acid-extractable (acid-soluble) amino acid pool in mammalian cells: 3 Competition for entry and its effects on incorporation into protein synthesis.

Competition studies have been carried out between normal and analogue amino acids with suspension cultured mammalian cells incubated, except for the competing amino acid, in normal medium. Although this produces less dramatic changes on uptake and incorporation than experiments performed in Krebs-Ringer solution, it has the advantage of obtaining data under more physiological conditions. A systematic survey with all the amino acids used has shown, in general, a non-specific interference for uptake into the acid-extractable pool, suggesting that a common pool-forming mechanism is involved. Individual differences in competitive behaviour probably arise from varying affinities of amino acids for the pool-forming mechanism, their ability to displace others from the pool, and the rate of their subsequent discharge, among other characteristics. Certain interactions appear exceptional, however, notably glycine and serine, which could be due to their linked metabolism. Incorporation of amino acids into protein of the same cells gave the anticipated high degree of specificity, but evidence is now presented that the amount of a particular labelled amino acid entering into protein depends not only on its absolute concentration in the medium, but also on its relative concentration. The results indicate that the effects of excesses of other amino acid is to reduce the probability with which the labelled species can be loaded by its own tRNA. This inhibition is of a non-specific nature.