GABA Metabolism in Saccharomyces cerevisiae

CORREA GARCIA SUSANA; BERMUDEZ MORETTI MARIANA

Gamma-Aminobutyric Acid (GABA): Biosynthesis, Medicinal Uses and Health Effects

Nova Publishers

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

The γ-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 tricarboxylic acid (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 to succinate by the succinate semialhehyde dehydrogenase. Then, succinate enters the TCA cycle. However, most of the incorporated GABA is not catabolized but accumulated in a subcellular compartment, like the vacuole. On the other hand, GABA is synthesized in yeast cells by the decarboxylation of glutamate as an intermediate of the GABA shunt, by which -ketoglutarate is converted to succinate. GABA shunt bypasses two steps of the TCA cycle and it is energetically less efficient than the direct oxidation of -ketoglutarate at the TCA cycle. Strong evidence suggests that the GABA shunt plays a crucial role in protecting cells from stress.