Glutamate decarboxylase. Substrate specificity and inhibition by carboxylic acids

Fonda, Margaret L.

doi:10.1021/bi00757a029

Cited by 66 publications

(44 citation statements)

References 24 publications

(17 reference statements)

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“…Of these two options, bacteria as the major source are more likely, because endogenous GABA production is restricted to selected endocrine cells within the epithelium and to neurons that have been proposed to play a role in tissue maturation and differentiation (Gilon et al 1987;Wang et al 2006). Moreover, both commensal and potentially pathogenic bacteria are well known for their ability to synthesize and release large amounts of GABA, especially under acidic stress to remove cytoplasmic protons (Fonda 1972;Gorden and Small 1993;Hersh et al 1996;Ueno et al 1997). Under the assumption that bacterial metabolites influence the expression of mucus and its components, respectively, the observation that germfree rodents are provided with less cecal goblet cells and non-goblet mucous-type cells than conventionally raised/conventionalized rodents (Kandori et al 1996;Ishikawa et al 1989) becomes plausible.…”

Section: Discussionmentioning

confidence: 99%

“…1), which, in turn, can be generated by the enzyme glutaminase (GLS) through the desamination of glutamine (Pinkus and Windmueller 1977). Isoforms of GAD are widely distributed throughout the animal and plant kingdom, from cockroach (Baxter and Torralba 1975) to Lactobacillus (Ueno et al 1997) and from Escherichia coli (Fonda 1972) to tomato (Akihiro et al 2008) and barley (Inatomi and Slaughter 1975). Accordingly, GABA is a natural component of the free amino acid pool of all kinds of ingested plants and probiotic/commensal bacteria in the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

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GABA selectively increases mucin-1 expression in isolated pig jejunum

et al. 2015

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The inhibitory neurotransmitter GABA (γ-aminobutyric acid) is synthesized by glutamic acid decarboxylase, which is expressed in the central nervous system and in various other tissues including the intestine. Moreover, GABA can be ingested in vegetarian diets or produced by bacterial commensals in the gastrointestinal tract. As previous studies in lung have suggested a link between locally increased GABA availability and mucin 5AC production, the present study sought to test whether the presence or lack of GABA (and its precursor glutamine) has an effect on intestinal mucin expression. Porcine jejunum epithelial preparations were incubated with two different amounts of GABA or glutamine on the mucosal side for 4 h, and changes in the relative gene expression of seven different mucins, enzymes involved in mucin shedding, GABA B receptor, enzymes involved in glutamine/GABA metabolism, glutathione peroxidase 2, and interleukin 10 were examined by quantitative PCR (TaqMan(®) assays). Protein expression of mucin-1 (MUC1) was analyzed by Western blot. On the RNA level, only MUC1 was significantly up-regulated by both GABA concentrations compared with the control. Glutamine-treated groups showed the same trend. On the protein level, all treatment groups showed a significantly higher MUC1 expression than the control group. We conclude that GABA selectively increases the expression of MUC1, a cell surface mucin that prevents the adhesion of microorganisms, because of its size and negative charge, and therefore propose that the well-described positive effects of glutamine on enterocytes and intestinal integrity are partly attributable to effects of its metabolite GABA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GABA selectively increases mucin-1 expression in isolated pig jejunum

et al. 2015

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“…37,38 Glu has three different ionisable groups, the a-carboxyl group (pK a = 2.2), carboxyl group (pK a = 4.3), a-amino group (pK a = 9.7). 37,38 Glu has three different ionisable groups, the a-carboxyl group (pK a = 2.2), carboxyl group (pK a = 4.3), a-amino group (pK a = 9.7).…”

Section: The Effect Of Ph On Glu Adsorption In [Al(oh)(l)] Nmentioning

confidence: 99%

l-Glutamic acid release from a series of aluminum-based isoreticular porous coordination polymers

et al. 2015

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We investigated the encapsulation of bioactive molecules such as L-glutamic acid (Glu) into a series of porous coordination polymers (PCPs) based on aluminum hydroxy dicarboxylates [Al(OH)(L)] n (L = dicarboxylate ligand) and the molecular release therefrom. The use of 2,6-naphthalene dicarboxylate (2,6-ndc), 1,4-benzene dicarboxylate (1,4-bdc) and 1,4-naphthalene dicarboxylate (1,4-ndc) as ligands allows us to systematically tune the pore size and the flexibility of frameworks while keeping the same topology and thus to investigate the effect of those parameters upon both adsorption and release of Glu. We revealed the impact of zwitterionic nature of Glu upon loading efficiency; optimal loading pH was shown to be that for which Glu bears both positive and negative charges. Whereas the loading capacity of PCPs is governed by the pore size ([Al(OH)(2,6-ndc)] n 4 [Al(OH)(1,4-bdc)] n 4 [Al(OH)(1,4ndc)] n ), the adsorption isotherm clearly revealed that small or flexible pores induce the stronger Glu-PCP interaction. The release experiments of Glu from PCPs in a physiological media (pH = 7.4, 37 1C) demonstrated the exceptional stabilization of Glu within [Al(OH)(1,4-bdc)] n , compared to those within the other frameworks; whereas the rigid frameworks of [Al(OH)(2,6-ndc)] n and [Al(OH)(1,4-ndc)] n spontaneously released almost the entire Glu contents within 10 h, 70% of Glu loaded within [Al(OH)(1,4-bdc)] n still remained therein over 24 h. Interestingly, the burst release of Glu was triggered by increasing temperature up to 80 1C, at which the framework changed its structure from a closed phase to the open phase.

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“…[27] Meanwhile, the l-glutamic acid decarboxylation reaction mixture contained 25 mM L-glutamic acid, 0.1 mM PLP, 1.25 U/mL of l-glutamic acid decarboxylase in pyridine-HCl buffer (0.1 M, pH 4.6). [28] The reactions were performed in duplicate in a final volume of 100 mL by incubation for 1 hour at 37 8C and 1200 rpm (Thermomixer comfort, Eppendorf). The reactions were stopped by the addition of 10 mL of trichloroacetic acid (aqueous solution 100% w/v) and centrifuged at 14000 rpm and 4 8C for 3 min.…”

Section: Enzyme Assaysmentioning

confidence: 99%

A High‐Throughput Screening Assay for Amino Acid Decarboxylase Activity

Médici¹,

Marı́a²,

Otten³

et al. 2011

Adv Synth Catal

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The development of sensitive and easy-toapply high-throughput screening methods is a common need in modern biocatalysis. With these powerful analytical tools in hands, chemists can easily assess enzyme libraries to identify either novel biocatalysts or improved mutants. Within biocatalysis, amino acid decarboxylases are gaining an increased importance, with several diverse applications ranging from the synthesis of bio-commodities to medical applications (e.g., synthesis of enzyme inhibitors at the level of l-DOPA decarboxylase). Herein, an efficient and simple analytical method for highthroughput screening of amino acid decarboxylase activity is reported. The method is valid for the discrimination of a broad range of amino acid/amine pairs such as l-tyrosine/tyramine, l-DOPA/dop-A C H T U N G T R E N N U N G amine, 5-hydroxy-l-tryptophan/serotonin, l-histidine/ histamine, l-serine/ethanolamine, l-tryptophan/tryptamine, l-glutamic acid/GABA, and l-alanine/ethyl-A C H T U N G T R E N N U N G amine. It has proven its versatility by using pure substrates, mixtures, or enzymatic reactions, both coming either from commercial enzymes or derived from cell-free (crude) extracts. The limit of detection was 13 mM for ethanolamine in the presence of 50 mM L-serine, while z' values were in the range 0.75-0.93, indicating the suitability for high-throughput screening.

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Glutamate decarboxylase. Substrate specificity and inhibition by carboxylic acids

Cited by 66 publications

References 24 publications

GABA selectively increases mucin-1 expression in isolated pig jejunum

GABA selectively increases mucin-1 expression in isolated pig jejunum

l-Glutamic acid release from a series of aluminum-based isoreticular porous coordination polymers

A High‐Throughput Screening Assay for Amino Acid Decarboxylase Activity

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