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Discovery and Background of GABA in Plants

Gubbi Vani Ishika1*, Deepthi Puttegowda1*, Ranjith Raj2, Manjunath Dammalli3, and Ramith Ramu1

1 Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India

2 Department of Pharmacology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570015, India

3 Department of Biotechnology, Siddaganga Institute of Technology, Tumkur, Karnataka, 572103, India

* Equal contribution

Abbreviations

ALMT

Aluminum‐activated malate transporters

GABA

Gamma‐aminobutyric acid

GAD

Glutamic acid decarboxylase

GHB

Gamma hydroxybutyrate

MDA

Malondialdehyde

ROS

Reactive oxygen species

SlGAD

Solanum lycopersicum glutamic acid decarboxylase

SSA

Succinic semialdehyde

Ssdh

Succinic semialdehyde dehydrogenase

TCAC

Tricarboxylic acid cycle

Introduction

Gamma‐aminobutyric acid (GABA) is a chemical that helps plants adapt to different growing conditions. GABA is a four‐carbon nonproteinogenic amino acid that is present in all plants and plant parts. It has been researched in both eukaryotes and prokaryotes. It was first identified in plants over seven decades ago in potato (Solanum tuberosum) tubers. Since then, extensive research has been conducted on its physiological significance, and it has been established that it functions as a signal molecule in plants in addition to being a metabolite. Food security and crop productivity are seriously at risk from the possible effects of climate change on plant development (Li et al. 2021). GABA is a four‐C, nonprotein amino acid that makes up 75% of the pool of free amino acids. Prokaryotic and eukaryotic species include GABA. Glutamic acid decarboxylase (GAD), an enzyme found in the cytosol, is the primary source of endogenous GABA. The so‐called GABA shunt, which is involved in a variety of physiological processes, including carbon flow into the tricarboxylic acid cycle (TCAC), cytosolic pH regulation, osmoregulation, signaling, and energy production, is how it is metabolized in the mitochondrial matrix (Shelp et al. 2017, 2021).

Its physiological function has been the subject of several research. Furthermore, it has been demonstrated that in plants, it serves as a signaling molecule as well as a metabolite. It has the ability to control plant growth and respond to both biotic and abiotic stresses, among other things (Seifikalhor et al. 2019). GABA functions as a signal for root growth, fruit ripening, pollen tube elongation (to enter the ovule), and seed germination in the context of Agrobacterium tumefaciens‐mediated plant gene transformation.

In response to drought stress, it emerges as a result of plant reactions that activate antioxidant enzymes and regulate stomatal opening; a high‐GABA concentration makes a plant more resilient to stress (Li et al. 2021). GABA's function in both stress‐adaptation (salinity, hypoxia/anoxia, drought, temperature, heavy metals, plant–insect interaction, and ROS‐related responses) and nonstress‐related biological pathways (e.g., plant–microbe interaction, contribution to the carbon and nitrogen metabolism, and regulation of signal transduction pathways) has been specifically highlighted (Seifikalhor et al. 2019 and Kaspal et al. 2021).

History

It was initially found that GABA was a naturally occurring compound in plants in the early to mid‐twentieth century, although the credit for its identification in plants goes to a number of researchers who studied different species of plants. The identification of GABA in plants is typically associated with the isolation and characterization of the compound in various plant tissues. These are some of the main figures who helped uncover GABA in plants. The year 1949 saw the discovery of it in plants (potato tuber) (Steward et al. 1949). However, later studies on animals showed that it was also significant in the brains of mammals as a neurotransmitter.

Research on plants gained additional speed when it was discovered that abiotic stress causes a rise in GABA concentration. The fact is that higher plants have been found to contain GABA, several animals, and bacteria as well as invertebrates. GABA was first identified in 1883 as a metabolic byproduct in microorganisms and plants. After the occurrence of GABA in potato tubers was confirmed in 1949, other reports of its presence in the brain emerged. Three distinct investigations on GABA in the mammalian central nervous system were given by Roberts and Frankel (1950) and Roberts (2007) in the same year in the same issue of Biological Chemistry.

Global experts are still working to establish GABA's status as an inhibitory neurotransmitter years later. Ernst Florey extracted a substance from horse brains in 1953 and administered it exogenously to cats and crayfish. They noticed inhibition in a few of their receptors in both studies and aversions. This substance was subsequently separated from the cow brain and recognized as GABA. It was also shown that artificially produced GABA inhibited the same crayfish receptors, confirming Florey's hypothesis that GABA functions in the brain as an inhibitory neurotransmitter. GABA was later proposed to serve as a metabolite and not be engaged in signaling because it is over 1000 times more abundant in the vertebrate brain than other neurotransmitters and participates in the Krebs cycle (GABA shunt). The lack of considerable GABA levels in invertebrates led to the conclusion that GABA is merely a metabolite and fails to meet the criteria for being a neurotransmitter (Florey and McLennan 1955).

Later studies on nematodes, however, demonstrated that GABA is, in fact, a potential neurotransmitter. The absence of it in invertebrates has been disproved by the discovery that it is also detected in crayfish and in larger quantities in Ascaris motor neurons. (Deo Rashmi et al. 2018). Ernest H. Wood and Albert F. Haight were among the first to identify and characterize GABA in plants in 1950. They described the presence of GABA in various plant tissues. Arthur M. Andrews and Ray B. Morrison in 1960 contributed to an understanding of GABA in plant tissues. The plasma membrane and organelle membranes are two examples of the membranes that GABA can pass through in a cell. Intercellular and intracellular GABA transport are also involved in this mechanism. It was not until 1999 that GABA transporters were found in plants, having first been identified in animals. According to Ramesh et al. (2018), Arabidopsis thaliana is one plant species that can effectively develop when given GABA as its main source of nitrogen (Ramesh et al. 2015). This suggests that plants do indeed have GABA transporters.

Background

The amino acid GABA, not part of the standard proteinogenic amino acids, was initially discovered in 1949 in potato tubers before its identification in animal brain extracts. Growing data in the 1950s and 1960s revealed that GABA may have an inhibitory neurotransmitter role in animals. It has been shown to inhibit crayfish stretch receptor neurons' impulses. However, GABA in mammalian nerve terminals was not identified until the study of Bloom and Iversen in 1971. About 10 years later, the activation of GABAA (ionotropic) and GABAB (metabotropic) receptors was found to be the primary mechanism responsible for GABA's inhibitory neurotransmitter effect. Mammals respond to excitatory neurotransmitters by activating GABAA receptors, which causes membrane hyperpolarization and a modest impact (Bloom and Iversen 1969; Watanabe and Fukuda 2015).

The regulation of brain function and development in mammals is greatly influenced by GABA receptors. Still, in addition to neural cells, these receptors have also been identified in human organs and other tissues. The role of GABA as an animal signaling molecule has been extensively studied after 50 years. In contrast, its comprehension in plants has primarily revolved (Bouch and Fromm 2004). Since the 1990s, there has been growing data that supports GABA's classification as a carbon–nitrogen metabolite and suggests that it may really serve as a signaling drug in plants. The evidence for this statement encompasses several factors, such as the presence of GABA concentration gradients, compartmentalized GABA metabolism, the fluctuating concentration of GABA in plant tissue, and its quick increase in response to different stimuli (Yue et al. 2014).

The control of the plant anion channel family ALMTs by GABA, for example, has led to new insights into the functions of GABA in plants. These insights suggest that changing anion flux across cell membranes is a means of translation of GABA metabolism into membrane signaling. The sequence similarity between animal GABAA receptors and ALMTs is minimal, yet GABA increases GABAA channel activity in mammals while inhibiting ALMT activity in plants. Nonetheless, this regulation leads to a relatively hyperpolarized state in both plant and animal cells Li et al. 2016; Nonaka et al. 2017). The alteration in membrane potential due to GABA in plants, influencing tissue growth, strongly indicates its signaling role in plants....