delta-Aminolevulinic acid uptake is mediated by the gamma-aminobutyric acid-specific permease UGA4

There is evidence that delta-aminolevulinic acid (ALA), a precursor of porphyrin biosynthesis, and gamma-aminobutyric acid (GABA) would be incorporated into yeast cells by a common permease. The purpose of this work was to confirm this hypothesis and to identify the shared permease. The transport of GABA in Saccharomyces cerevisiae is mediated by three permeases: the general amino acid permease (GAP1), the specific proline permease (PUT4) and a fairly specific GABA permease (UGA4). To determine which of these permeases is also involved in ALA uptake, ALA and GABA incorporations were measured in strains lacking GAP1, UGA4 or GAP1 and UGA4 permeases. Results indicated that ALA is mainly incorporated by UGA4. This was also confirmed by regulatory studies, since ALA uptake was induced by GABA, and it is well known that UGA4 permease is induced by GABA. On the other hand, ALA did not induce the synthesis of this permease. Therefore, we demonstrate here that ALA, which cannot be used as a nitrogen source, is uptaken by S. cerevisiae cells mainly using a permease encoded by a gene subjected to a regulation typical of several nitrogen genes.