New Insights into γ-Aminobutyric Acid Catabolism: Evidence for γ-Hydroxybutyric Acid and Polyhydroxybutyrate Synthesis inSaccharomyces cerevisiae

Abstract

The ␥-aminobutyrate (GABA) shunt, an alternative route for the conversion of ␣-ketoglutarate to succinate, involves the glutamate decarboxylase Gad1p, the GABA transaminase Uga1p and the succinate semialdehyde dehydrogenase Uga2p. This pathway has been extensively described in plants and animals, but its function in yeast remains unclear. We show that the flux through Gad1p is insignificant during fermentation in rich sugar-containing medium, excluding a role for this pathway in redox homeostasis under anaerobic conditions or sugar stress. However, we found that up to 4 g of exogenous GABA/liter was efficiently consumed by yeast. We studied the fate of this consumed GABA. Most was converted into succinate, with a reaction yield of 0.7 mol/mol. We also showed that a large proportion of GABA was stored within cells, indicating a possible role for this molecule in stress tolerance mechanisms or nitrogen storage. Furthermore, based on enzymatic and metabolic evidence, we identified an alternative route for GABA catabolism, involving the reduction of succinate-semialdehyde into ␥-hydroxybutyric acid and the polymerization of ␥-hydroxybutyric acid to form poly-(3-hydroxybutyric acid-co-4-hydroxybutyric acid). This study provides the first demonstration of a native route for the formation of this polymer in yeast. Our findings shed new light on the GABA pathway and open up new opportunities for industrial applications.

Sporadic Alzheimer's Disease: The Starving Brain

“…2). This metabolic pathway is conserved from bacteria through protozoa, plants, and vertebrates [53][54][55][56]. It involves 3 enzymes: glutamate decarboxylase, which catalyzes the decarboxylation of glutamate to GABA; GABA transaminase, which converts GABA to succinic semialdehyde (SSA); and SSA dehydrogenase (SSADH), which catalyzes the oxidation of SSA to succinate.…”

“…Levels of GHB are very low in whole adult rat brain, in the 2 nmol/gm range, and in the 13 nmol/gm range in postmortem human frontal cortex [61]. The function of these very low GHB tissue levels is not known [22,62,63], but a clue may be discerned from yeast which polymerizes GHB and stores it as a polymer containing units of beta-hydroxybutyrate (BHB) and GHB [54]. Other microorganisms have also been shown to incorporate GHB into a polymer under experimental conditions [64].…”

Microbial Carbon Substrate Utilization Differences among High- and Average-Yield Soybean Areas

“…Another pathway for α-ketobutyric acid is eventually entering the citric acid cycle [35]. One carboxylic acid that had a large contribution to PC 1 from HY areas was γ-hydroxybutyric acid, which is a derivative of butyric acid, also known as butanoic acid or BTA, and a product of anaerobic fermentation [36]. The other carboxylic acid that had a large contribution to PC 2 from HY areas was pyruvic acid methyl ester, the ester of pyruvic acid, which is also an intermediate in the citric acid cycle [35].…”

Genome Structure ofBacillus cereustsu1 and Genes Involved in Cellulose Degradation and Poly-3-Hydroxybutyrate Synthesis

“…Some of these amino acids can potentially be converted into PHB through various alternative pathways (see Figure S4 in Supplementary Material). In a previous study [62] Raman spectra: 300 to 2200 cm TCA cycle into P4HB/PH3B/P(3HB-co-4HB) [63]. P(3HB-co-4HB)-like copolymer was found in B. cereus SPV.…”