GABA Metabolism in Saccharomyces cerevisiae

CORREA GARCIA SUSANA; BERMUDEZ MORETTI MARIANA

Gamma-aminobutyric acid (GABA) Biosynthesis, Medicinal Uses and Health Effects

NOVA Science publishers

Lugar: New York; Año: 2014; p. 13 - 28

The gamma-aminobutyric acid (GABA) is a non protein amino acid present in bacteria, plants, fungi and even in vertebrates. The role of GABA in the budding yeast Saccharomyces cerevisiae is not fully understood. GABA can be used by yeast as the sole nitrogen source and its carbon backbone enters the TCA cycle. Three permeases are involved in extracellular GABA uptake: the general amino acid permease Gap1, the proline-specific permease Put4 and the GABA-specific permease Uga4. Once within the cell GABA is deaminated by the enzyme GABA transaminase yielding glutamate and succinate semialdehyde. Glutamate enters the central nitrogen metabolism while succinate semialdehyde is converted by the succinate semialhehyde dehydrogenase to succinate that enters the TCA cycle. However, most of the uptaken GABA is not catabolyzed but accumulated in a subcellular compartment, likely the vacuole. On the other hand, GABA is synthesized in yeast cell by the decarboxylation of glutamate as an intermediate of the GABA shunt, by which alpha-ketoglutarate is converted to succinate bypassing the TCA step that involves the alpha-ketoglutarate dehydrogenase. The GABA shunt is energetically less efficient than the direct oxidation of alpha-ketoglutarate al the TCA. Strong evidence suggests that the GABA shunt plays a crucial role in protecting cells from stress.