Biosynthesis, Metabolism, and Physiological Functions of Gamma-Aminobutyric Acid

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Microbiology and Ecological Metabolomics".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 17742

Special Issue Editors

1. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
2. Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, China
Interests: microbiology; metabolites; gamma-aminobutyric acid; biosynthesis; molecular biology
1. College of Life Sciences and Engineering, Northwest Minzu University, Lanzhou 730030, China
2. China-Malaysia National Joint Laboratory, Northwest Minzu University, Lanzhou 730030, China
Interests: lactic acid bacteria; gamma-aminobutyric acid; antioxidant; physiological functions

Special Issue Information

Dear Colleagues,

Gamma-aminobutyric acid (GABA) is a non-proteinogenic amino acid that is extensively distributed in various organisms. As an important bioactive molecule, GABA acts as the major inhibitory neurotransmitter in mammals and has many other biological effects. Therefore, GABA has been widely used in the food and pharmaceutical industries. To date, GABA has become a star metabolite, garnering attention from diverse aspects.   

This Special Issue of Metabolites is dedicated to new findings associated with the biosynthesis, metabolism, and physiological activities of GABA. Submissions of original research articles and reviews are welcome. Topics may include, but are not limited to, the aforementioned aspects of GABA. Relevant methodological advances will also be considered. In this Special Issue, we aim to gather groundbreaking contributions to the related fields.

Prof. Dr. Haixing Li
Prof. Dr. Dandan Gao
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gamma-aminobutyric acid
  • metabolism and metabolomics
  • biotechnology and bioengineering
  • biosynthesis
  • physiological function
  • gamma-aminobutyric acid-producing microbes
  • methodology

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 2594 KiB  
Article
Exogenous γ-Aminobutyric Acid (GABA) Enhanced Response to Abiotic Stress in Hypsizygus marmoreus by Improving Mycelial Growth and Antioxidant Capacity
by Zhi Cao, Hongyu Chen, Chenli Zhou, Ming Gong, Yan Li, Youran Shao, Yingying Wu and Dapeng Bao
Metabolites 2024, 14(2), 94; https://doi.org/10.3390/metabo14020094 - 27 Jan 2024
Viewed by 1078
Abstract
γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous [...] Read more.
γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses. Full article
Show Figures

Graphical abstract

12 pages, 1694 KiB  
Article
Genetic Circuits for Feedback Control of Gamma-Aminobutyric Acid Biosynthesis in Probiotic Escherichia coli Nissle 1917
by Matthew Lebovich, Marcos A. Lora, Jared Gracia-David and Lauren B. Andrews
Metabolites 2024, 14(1), 44; https://doi.org/10.3390/metabo14010044 - 11 Jan 2024
Viewed by 1049
Abstract
Engineered microorganisms such as the probiotic strain Escherichia coli Nissle 1917 (EcN) offer a strategy to sense and modulate the concentration of metabolites or therapeutics in the gastrointestinal tract. Here, we present an approach to regulate the production of the depression-associated metabolite gamma-aminobutyric [...] Read more.
Engineered microorganisms such as the probiotic strain Escherichia coli Nissle 1917 (EcN) offer a strategy to sense and modulate the concentration of metabolites or therapeutics in the gastrointestinal tract. Here, we present an approach to regulate the production of the depression-associated metabolite gamma-aminobutyric acid (GABA) in EcN using genetic circuits that implement negative feedback. We engineered EcN to produce GABA by overexpressing glutamate decarboxylase and applied an intracellular GABA biosensor to identify growth conditions that improve GABA biosynthesis. We next employed characterized genetically encoded NOT gates to construct genetic circuits with layered feedback to control the rate of GABA biosynthesis and the concentration of GABA produced. Looking ahead, this approach may be utilized to design feedback control of microbial metabolite biosynthesis to achieve designable smart microbes that act as living therapeutics. Full article
Show Figures

Figure 1

16 pages, 5316 KiB  
Article
Dietary Coated Sodium Butyrate Ameliorates Hepatic Lipid Accumulation and Inflammation via Enhancing Antioxidative Function in Post-Peaking Laying Hens
by Sasa Miao, Yan Li, Tianming Mu, Xiaoming Wang, Wenyan Zhao, Ru Li, Xinyang Dong and Xiaoting Zou
Metabolites 2023, 13(5), 650; https://doi.org/10.3390/metabo13050650 - 10 May 2023
Cited by 4 | Viewed by 1673
Abstract
During the aging process of laying hens, hepatic oxidative stress damage and lipid accumulation are prone to occur, leading to the deterioration of egg quality and a decline in production properties. This research was designed to explore the effects of different levels of [...] Read more.
During the aging process of laying hens, hepatic oxidative stress damage and lipid accumulation are prone to occur, leading to the deterioration of egg quality and a decline in production properties. This research was designed to explore the effects of different levels of coated sodium butyrate (CSB) addition on oxidation resistance, inflammatory reaction, lipid metabolism and hepatic oxidative damage-related gene expression in aged laying hens. A total of 720 healthy 52 weeks old Huafeng laying hens were arbitrarily divided into 5 groups of 6 replicates with 24 birds each and fed a basal diet supplemented with 0, 250, 500, 750 and 1000 mg/kg CSB for 8 weeks, respectively. The CSB quadratically upgraded GSH-Px activities and downgraded MDA content in the liver and serum. The LDL-C, NEFA and TG contents decreased quadratically in CSB groups and significantly reduced the fatty vacuoles as well as the formation of fat granules in the liver (p < 0.05). Meanwhile, the CSB quadratically upregulated the gene expression of IL-10, Nrf2 and HO1, but downregulated the gene expression of IFN-γ, TNF-α and Keap1 in a quadratic manner (p < 0.05). Moreover, the CSB quadratically degraded the mRNA level of fatty acid synthesis but increased the gene level of key enzymes of fatty acid catabolism (p < 0.05). In conclusion, dietary CSB supplementation has a favorable effect in protecting against liver injury and alleviating lipid accumulation and inflammation by enhancing hepatic antioxidative function in aged laying hens. Full article
Show Figures

Figure 1

15 pages, 666 KiB  
Article
Interactive Effect of Dietary Gamma-Aminobutyric Acid (GABA) and Water Temperature on Growth Performance, Blood Plasma Indices, Heat Shock Proteins and GABAergic Gene Expression in Juvenile Olive Flounder Paralichthys olivaceus
by Seunghan Lee, Mohammad Moniruzzaman, Nathaniel Farris, Taesun Min and Sungchul C. Bai
Metabolites 2023, 13(5), 619; https://doi.org/10.3390/metabo13050619 - 30 Apr 2023
Cited by 3 | Viewed by 2680
Abstract
Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system of living organisms and has the ability to reduce the magnitude of stress in humans and animals. In this study, we evaluated the supplemental effects of GABA on normal and [...] Read more.
Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system of living organisms and has the ability to reduce the magnitude of stress in humans and animals. In this study, we evaluated the supplemental effects of GABA on normal and high water temperature based on growth, blood plasma composition as well as heat shock proteins and GABA-related gene expression in juvenile olive flounder. For this, a 2 × 2 factorial design of experiment was employed to investigate the dietary effects of GABA at 0 mg/kg of diet (GABA0 diet) and 200 mg/kg of diet (GABA200 diet) in water temperatures of 20 ± 1 °C (normal temperature) and 27 ± 1 °C (high temperature) for 28 days. A total of 180 fish with an average initial weight of 40.1 ± 0.4 g (mean ± SD) were distributed into 12 tanks, of which, each tank contained 15 fish based on the 4 dietary treatment groups in triplicate. At the end of the feeding trial, the results demonstrated that both temperature and GABA had significant effects on the growth performance of the fish. However, fish fed the GABA200 diet had a significantly higher final body weight, weight gain and specific growth rate as well as a significantly lower feed conversion ratio than the fish fed the GABA0 diet at the high water temperature. A significant interactive effect of water temperature and GABA was observed on the growth performance of olive flounder based on the two-way analysis of variance. The plasma GABA levels in fish were increased in a dose-dependent manner at normal or high water temperatures, whereas cortisol and glucose levels were decreased in fish fed GABA-supplemented diets under temperature stress. The GABA-related mRNA expression in the brains of the fish such as GABA type A receptor-associated protein (Gabarap), GABA type B receptor 1 (Gabbr1) and glutamate decarboxylase 1 (Gad1) were not significantly affected by GABA-supplemented diets under normal or temperature stressed conditions. On the other hand, the mRNA expression of heat shock proteins (hsp) in the livers of the fish, such as hsp70 and hsp90, were unchanged in fish fed the GABA diets compared to the control diet at the high water temperature. Collectively, the present study showed that dietary supplementation with GABA could enhance growth performance, and improve the feed utilization, plasma biochemical parameters and heat shock proteins and GABA-related gene expression under the stress of high water temperatures in juvenile olive flounder. Full article
Show Figures

Figure 1

13 pages, 9723 KiB  
Article
Sodium-Ion-Free Fermentative Production of GABA with Levilactobacillus brevis CD0817
by Haixing Li, Jinfeng Pei, Cheng Wei, Zhiyu Lin, Hao Pan, Zhenkang Pan, Xinyue Guo and Zhou Yu
Metabolites 2023, 13(5), 608; https://doi.org/10.3390/metabo13050608 - 28 Apr 2023
Cited by 3 | Viewed by 1054
Abstract
Gamma-aminobutyric acid (GABA) has positive effects on many physiological processes. Lactic acid bacterial production of GABA is a future trend. This study aimed to produce a sodium-ion-free GABA fermentation process for Levilactobacillus brevis CD0817. In this fermentation, both the seed and fermentation media [...] Read more.
Gamma-aminobutyric acid (GABA) has positive effects on many physiological processes. Lactic acid bacterial production of GABA is a future trend. This study aimed to produce a sodium-ion-free GABA fermentation process for Levilactobacillus brevis CD0817. In this fermentation, both the seed and fermentation media used L-glutamic acid instead of monosodium L-glutamate as the substrate. We optimized the key factors influencing GABA formation, adopting Erlenmeyer flask fermentation. The optimized values of the key factors of glucose, yeast extract, Tween 80, manganese ion, and fermentation temperature were 10 g/L, 35 g/L, 1.5 g/L, 0.2 mM, and 30 °C, respectively. Based on the optimized data, a sodium-ion-free GABA fermentation process was developed using a 10-L fermenter. During the fermentation, L-glutamic acid powder was continuously dissolved to supply substrate and to provide the acidic environment essential for GABA synthesis. The current bioprocess accumulated GABA at up to 331 ± 8.3 g/L after 48 h. The productivity of GABA was 6.9 g/L/h and the molar conversion rate of the substrate was 98.1%. These findings demonstrate that the proposed method is promising in the fermentative preparation of GABA by lactic acid bacteria. Full article
Show Figures

Graphical abstract

12 pages, 4272 KiB  
Article
Sensitivity Intensified Ninhydrin-Based Chromogenic System by Ethanol-Ethyl Acetate: Application to Relative Quantitation of GABA
by Haixing Li, Lingqin Wang, Lijuan Nie, Xiaohua Liu and Jinheng Fu
Metabolites 2023, 13(2), 283; https://doi.org/10.3390/metabo13020283 - 16 Feb 2023
Cited by 3 | Viewed by 1513
Abstract
Gamma-aminobutyric acid (GABA) is a functional metabolite in various organisms. Herein, a sensitivity intensified ninhydrin-based chromogenic system (SINICS), achieved by ethanol and ethyl acetate, is described for the reliable relative quantitation of GABA. A 2.9 mL SINICS kit comprises 1% ninhydrin, 40% ethanol, [...] Read more.
Gamma-aminobutyric acid (GABA) is a functional metabolite in various organisms. Herein, a sensitivity intensified ninhydrin-based chromogenic system (SINICS), achieved by ethanol and ethyl acetate, is described for the reliable relative quantitation of GABA. A 2.9 mL SINICS kit comprises 1% ninhydrin, 40% ethanol, 25% ethyl acetate, and 35 μL 0.2 M sodium acetate buffer (pH 5.0). In practice, following the addition of a 0.1 mL sample to the kit, the chromogenic reaction is completed by heating at 70 °C for 30 min. The kit increased the color development sensitivity of L-glutamic acid and GABA, with the detection limits being reduced from 20 mM and 200 mM to 5 mM and 20 mM, respectively. The chromophore was stable for at least 2 h at room temperature, which was sufficient for a routine colorimetric analysis. The absorbance at 570 nm with the deduction of background directly represents the content of amino acid. For a proof-of-concept, the SINICS was adopted to optimize the GABA fermentation process of Levilactobacillus brevis CD0817. The results demonstrated that SINICS is an attractive alternative to the available ninhydrin-based colorimetric methods. Full article
Show Figures

Figure 1

18 pages, 38737 KiB  
Article
Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice
by Feng-Ling Wu, Si-Hai Chen, Jia-Ni Li, Liu-Jie Zhao, Xue-Mei Wu, Jie Hong, Ke-Hua Zhu, Han-Xue Sun, Su-Juan Shi, E Mao, Wei-Dong Zang, Jing Cao, Zhen-Zhen Kou and Yun-Qing Li
Metabolites 2023, 13(2), 226; https://doi.org/10.3390/metabo13020226 - 03 Feb 2023
Cited by 3 | Viewed by 1777
Abstract
Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma–aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR–PVT pathway participates in nociceptive modulation is still [...] Read more.
Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma–aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR–PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+–PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+–PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+–PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission. Full article
Show Figures

Figure 1

Review

Jump to: Research

17 pages, 1976 KiB  
Review
Role of Gamma-Aminobutyric Acid in Plant Defense Response
by Zhujuan Guo, Junqing Gong, Shuitian Luo, Yixin Zuo and Yingbai Shen
Metabolites 2023, 13(6), 741; https://doi.org/10.3390/metabo13060741 - 10 Jun 2023
Cited by 4 | Viewed by 1275
Abstract
Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that acts as a defense substance and a signaling molecule in various physiological processes, and which helps plants respond to biotic and abiotic stresses. This review focuses on the role of GABA’s synthetic and [...] Read more.
Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that acts as a defense substance and a signaling molecule in various physiological processes, and which helps plants respond to biotic and abiotic stresses. This review focuses on the role of GABA’s synthetic and metabolic pathways in regulating primary plant metabolism, redistributing carbon and nitrogen resources, reducing the accumulation of reactive oxygen species, and improving plants’ tolerance of oxidative stress. This review also highlights the way in which GABA maintains intracellular pH homeostasis by acting as a buffer and activating H+-ATPase. In addition, calcium signals participate in the accumulation process of GABA under stress. Moreover, GABA also transmits calcium signals through receptors to trigger downstream signaling cascades. In conclusion, understanding the role of GABA in this defense response provides a theoretical basis for applying GABA in agriculture and forestry and feasible coping strategies for plants in complex and changeable environments. Full article
Show Figures

Figure 1

11 pages, 1302 KiB  
Review
Metabolic Role of GABA in the Secretory Function of Pancreatic β-Cells: Its Hypothetical Implication in β-Cell Degradation in Type 2 Diabetes
by Jorge Tamarit-Rodriguez
Metabolites 2023, 13(6), 697; https://doi.org/10.3390/metabo13060697 - 27 May 2023
Cited by 1 | Viewed by 1192
Abstract
The stimulus-secretion coupling of a glucose-induced release is generally attributed to the metabolism of the hexose in the β-cells in the glycolytic pathway and the citric acid cycle. Glucose metabolism generates an increased cytosolic concentration of ATP and of the ATP/ADP ratio that [...] Read more.
The stimulus-secretion coupling of a glucose-induced release is generally attributed to the metabolism of the hexose in the β-cells in the glycolytic pathway and the citric acid cycle. Glucose metabolism generates an increased cytosolic concentration of ATP and of the ATP/ADP ratio that closes the ATP-dependent K+-channel at the plasma membrane. The resultant depolarization of the β-cells opens voltage-dependent Ca2+-channels at the plasma membrane that triggers the exocytosis of insulin secretory granules. The secretory response is biphasic with a first and transient peak followed by a sustained phase. The first phase is reproduced by a depolarization of the β-cells with high extracellular KCl maintaining the KATP-channels open with diazoxide (triggering phase); the sustained phase (amplifying phase) depends on the participation of metabolic signals that remain to be determined. Our group has been investigating for several years the participation of the β-cell GABA metabolism in the stimulation of insulin secretion by three different secretagogues (glucose, a mixture of L-leucine plus L-glutamine, and some branched chain alpha-ketoacids, BCKAs). They stimulate a biphasic secretion of insulin accompanied by a strong suppression of the intracellular islet content of gamma-aminobutyric acid (GABA). As the islet GABA release simultaneously decreased, it was concluded that this resulted from an increased GABA shunt metabolism. The entrance of GABA into the shunt is catalyzed by GABA transaminase (GABAT) that transfers an amino group between GABA and alpha-ketoglutarate, resulting in succinic acid semialdehyde (SSA) and L-glutamate. SSA is oxidized to succinic acid that is further oxidized in the citric acid cycle. Inhibitors of GABAT (gamma-vinyl GABA, gabaculine) or glutamic acid decarboxylating activity (GAD), allylglycine, partially suppress the secretory response as well as GABA metabolism and islet ATP content and the ATP/ADP ratio. It is concluded that the GABA shunt metabolism contributes together with the own metabolism of metabolic secretagogues to increase islet mitochondrial oxidative phosphorylation. These experimental findings emphasize that the GABA shunt metabolism is a previously unrecognized anaplerotic mitochondrial pathway feeding the citric acid cycle with a β-cell endogenous substrate. It is therefore a postulated alternative to the proposed mitochondrial cataplerotic pathway(s) responsible for the amplification phase of insulin secretion. It is concluded the new postulated alternative suggests a possible new mechanism of β-cell degradation in type 2 (perhaps also in type 1) diabetes. Full article
Show Figures

Figure 1

18 pages, 1035 KiB  
Review
GABA Metabolism, Transport and Their Roles and Mechanisms in the Regulation of Abiotic Stress (Hypoxia, Salt, Drought) Resistance in Plants
by Ding Yuan, Xiaolei Wu, Binbin Gong, Ruixiao Huo, Liran Zhao, Jingrui Li, Guiyun Lü and Hongbo Gao
Metabolites 2023, 13(3), 347; https://doi.org/10.3390/metabo13030347 - 26 Feb 2023
Cited by 9 | Viewed by 3059
Abstract
γ- Aminobutyric acid (GABA) is a ubiquitous four-carbon non-protein amino acid. In plants, GABA is found in different cell compartments and performs different metabolic functions. As a signalling molecule, GABA participates in the regulation of tolerance to various abiotic stresses. Many research studies [...] Read more.
γ- Aminobutyric acid (GABA) is a ubiquitous four-carbon non-protein amino acid. In plants, GABA is found in different cell compartments and performs different metabolic functions. As a signalling molecule, GABA participates in the regulation of tolerance to various abiotic stresses. Many research studies have found that GABA accumulates in large amounts when plants are subjected to abiotic stress, which have been demonstrated through the Web of Science, PubMed, Elsevier and other databases. GABA enhances the tolerance of plants to abiotic stress by regulating intracellular pH, ion transport, activating antioxidant systems and scavenging active oxygen species. In the process of GABA playing its role, transport is very important for the accumulation and metabolism pathway of GABA in cells. Therefore, the research on the transport of GABA across the cell membrane and the organelle membrane by transport proteins is a direction worthy of attention. This paper describes the distribution, biosynthesis and catabolism of GABA in plants. In addition, we focus on the latest progress in research on the transport of exogenous GABA and on the function and mechanism in the regulation of the abiotic stress response. Based on this summary of the role of GABA in the resistance to various abiotic stresses, we conclude that GABA has become an effective compound for improving plant abiotic tolerance. Full article
Show Figures

Graphical abstract

Back to TopTop