The γ-aminobutyric acid (GABA) is a non-proteic aminoacid synthesized by almost all living organisms. GABA metabolism, known as “GABA shunt” involves three enzymes: glutamate decarboxylase (GAD), GABA aminotransferase (GAT) and succinate semialdehyde dehydrogenasi (SSADH). These three enzymes act in concert to convert glutamate (α-ketoglutarate) to succinate, bypassing two reactions of the tricarboxylic acid cycle. The GABA shunt pathway is well conserved from bacteria, fungi and plants through vertebrates with different biological function in each organism [1] [2]. In mammals, GABA has two different roles: inhibitory neurotransmitter and trophic factor during central nervous system (CNS) development. In plants, the GABA shunt appears to contribute to the control of cytosolic pH, balance between carbon and nitrogen metabolism and to stress response. In some of enteric bacteria GABA is a metabolic product inside the cell and it is involved in acid resistance system. GABA has also been shown to play a potential signalling role in biological and developmental processes, i.g. it has been found as signalling molecule during host-pathogen interactions and during yeast colony development [3]. In the yeast Saccharomyces cerevisiae, the deletion of UGA3 gene -which encodes a zinc-finger transcription factor necessary for GABA-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes- extends replicative lifespan, as did deletion of UGA1 and GAD1 (glutamate decarboxylase); in contrast strains with UGA2 or UGA4 deletions exhibited no lifespan extensions. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. [1]. Nevertheless, the effects of these enzymes on chronological lifespan and stress response have not been studied yet. Data on the role of GABA shunt in budding yeast during CLS and under stress conditions will be presented. References: [1] Cao J., Barbosa J.M., Singh N.K. and Locy R.D. (2013), Yeast, (4):129-44. [2] Kamei Y., Tamura T., Yoshida R., Ohta S., Fukusaki E. and Mukai Y. (2011), Biochem Biophys Res Commun, 407(1):185-90. [3] Cáp M, Stěpánek L, Harant K, Váchová L, Palková Z. (2012), Mol Cell. 25;46(4):436-48
Role of GABA metabolism enzymes during stress, aging and apoptosis in budding yeast, Saccharomyces cerevisiae / Stirpe, Mariarita; Palermo, Vanessa; Falcone, Claudio; Mazzoni, Cristina. - (2014). (Intervento presentato al convegno Cell Stress: Survival and Apoptosis (CSSA 2014) tenutosi a Bertinoro (FC) nel 30-31 May).
Role of GABA metabolism enzymes during stress, aging and apoptosis in budding yeast, Saccharomyces cerevisiae
STIRPE, MARIARITA;PALERMO, Vanessa;FALCONE, Claudio;MAZZONI, Cristina
2014
Abstract
The γ-aminobutyric acid (GABA) is a non-proteic aminoacid synthesized by almost all living organisms. GABA metabolism, known as “GABA shunt” involves three enzymes: glutamate decarboxylase (GAD), GABA aminotransferase (GAT) and succinate semialdehyde dehydrogenasi (SSADH). These three enzymes act in concert to convert glutamate (α-ketoglutarate) to succinate, bypassing two reactions of the tricarboxylic acid cycle. The GABA shunt pathway is well conserved from bacteria, fungi and plants through vertebrates with different biological function in each organism [1] [2]. In mammals, GABA has two different roles: inhibitory neurotransmitter and trophic factor during central nervous system (CNS) development. In plants, the GABA shunt appears to contribute to the control of cytosolic pH, balance between carbon and nitrogen metabolism and to stress response. In some of enteric bacteria GABA is a metabolic product inside the cell and it is involved in acid resistance system. GABA has also been shown to play a potential signalling role in biological and developmental processes, i.g. it has been found as signalling molecule during host-pathogen interactions and during yeast colony development [3]. In the yeast Saccharomyces cerevisiae, the deletion of UGA3 gene -which encodes a zinc-finger transcription factor necessary for GABA-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes- extends replicative lifespan, as did deletion of UGA1 and GAD1 (glutamate decarboxylase); in contrast strains with UGA2 or UGA4 deletions exhibited no lifespan extensions. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. [1]. Nevertheless, the effects of these enzymes on chronological lifespan and stress response have not been studied yet. Data on the role of GABA shunt in budding yeast during CLS and under stress conditions will be presented. References: [1] Cao J., Barbosa J.M., Singh N.K. and Locy R.D. (2013), Yeast, (4):129-44. [2] Kamei Y., Tamura T., Yoshida R., Ohta S., Fukusaki E. and Mukai Y. (2011), Biochem Biophys Res Commun, 407(1):185-90. [3] Cáp M, Stěpánek L, Harant K, Váchová L, Palková Z. (2012), Mol Cell. 25;46(4):436-48I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
