Glutamate Decarboxylase
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
Zinc acetate is the most potent inhibitor among the divalent cations tested, inhibiting to the extent of 50%, at 10 μΜ concentration, followed by the acetates of Cd2+, Hg2+, and Cu2+. The remaining divalent cations are far less effective as inhibitors. The percentages of inhibition by these divalent cations at 10 mM concentration are as follows: Ni2+, 90%; Mn2+ and Co2+, 80%; Ba2+, 75%; Ca2+, 50%; Mg2+ ,45%; and Sr2+, 30%. The decreasing order of inhibitory potency is Zn2+ > Cd2+ , Hg2+, Cu2+ > Ni2+ > Mn2+, Co2+ > Ba2+ > Ca2+ > Mg2+ > Sr2+. The rat brain GAD, similar to the mouse brain enzyme, is sensitive to various inhibitors. Inhibition of 50% of the rat brain GAD activity occurred at the following concentrations for each inhibitor: DTNB, 2.5 μΜ; aminooxyacetic acid (AOAA), 1 μΜ; 3-mercaptopropionic acid, 15 μΜ; zinc acetate, 25 μΜ; NaCl, 17.5 mM; α-ketoglutarate, 9 mM; and β-methylene-D,l-aspartate, 0.1 mM. Other physiological substances such as mono-and dicarboxylic acids, nucleotides, and biogenic amines are all moderate to weak inhibitors. However, no activator for the neuronal GAD has been found yet.
Morphoregulatory Role Of Hydroxyproline-Containing Proteins In Liverworts
R. N. Chopra, Satish C. Bhatla in Bryophyte Development: Physiology and Biochemistry, 2019
To test this idea, antagonists of ethylene synthesis37,38 and ethylene action39 were used in experiments to find out if interfering with the synthesis or action of ethylene would concomitantly interfere with the morphoregulatory function of Hyp-protein (i.e., suppression). The antagonists of ethylene synthesis used were α-aminooxyacetic acid (AOA) and aminoethoxyvinylglycine (AVG). The antagonist of ethylene action used was silver nitrate. The results of these experiments supported our idea.40 All three ethylene antagonists prevented the suppressed cell proliferation of specific leaf primordia (Figure 10). It appeared, then, that ethylene and Hyp-protein somehow act in an interrelated way to regulate cell proliferation. We assumed that we had identified molecules that functioned importantly to regulate when and how proliferation of cells is suppressed. Of our three questions, what regulatory factors determine how, when, and where cell proliferation is suppressed, one remained — what determines where suppressed cell proliferation occurs? Once ethylene was implicated, a possible candidate for regulating where ethylene synthesis might be induced quickly came to mind. Following the first report that native auxin, indole-3-acetic acid (IAA), " . . . accelerates the release of ethylene",41 it had become well established that growth-suppressing levels of ethylene are often triggered by auxin.42,43 Moreover, the transport of auxin is strongly directional and highly regulated in plants.44 In short, it seemed to us that the phytohormone triggering ethylene-mediated suppression of leaf primordia in leafy liverworts might be the same one that triggers ethylene-mediated suppression of localized growth in dominance and tropic phenomena.44,45
SREKA-targeted liposomes for highly metastatic breast cancer therapy
Published in Drug Delivery, 2023
Balázs Vári, Levente Dókus, Adina Borbély, Anikó Gaál, Diána Vári-Mező, Ivan Ranđelović, Anna Sólyom-Tisza, Zoltán Varga, Norbert Szoboszlai, Gábor Mező, József Tóvári
Solvents for the syntheses and purification were obtained from Reanal (Budapest, Hungary) or VWR International Kft. (Debrecen, Hungary). All amino acid derivatives used for the synthesis of peptides and Fmoc-Rink-amide MBHA resin were purchased from Iris Biotech GmbH (Marktredwitz, Germany). Reagents applied for SPPS [N,N′-diisopropylcarbodiimide (DIC), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1-hydroxybenzotriazole hydrate (HOBt), triisopropylsilane (TIS)], ninhydrin, acetic anhydride, N,N-diisopropylethylamine were delivered by Sigma-Aldrich, St. Louis, Missouri, USA. Aminooxyacetic acid and methoxyamine were TCI (Tokyo, Japan) products. Daunomycin was donated from IVAX (Budapest Hungary). The PEGylated phospholipid derivatives were purchased from Biopharma PEG (Watertown, USA).
Exploring the beneficial effects and possible mechanisms of repeated episodes of whole-body hypoxic perconditioning in rat model of preeclampsia
Published in Hypertension in Pregnancy, 2020
Yan Li, Chunyun Wang, Jing Wang, Leisi Tao
In the present study, administration of a CBS inhibitor, i.e.,, amino-oxyacetic acid (25 and 50 mg/kg) significantly abolished the beneficial effects of three episodes of hypoxic perconditioning in L-NAME-treated pregnant rats and its administration was associated with a significant increase in SBP, urinary protein, nephrin, and podocin levels, measured on the different days of gestation. Furthermore, it abolished the effects of three episodes of hypoxic perconditioning on the cystathionine-β-synthase levels in L-NAME-treated pregnant rats, with no effect on the cystathionine-γ-lyase. In addition, administration of amino-oxyacetic acid abolished hypoxic perconditioning-induced increase in the H2 S levels in L-NAME-treated rats (Figure 2(b), 3(b), 4(b), 5(b), 6(b), 7(b), 8(b) and 9(b)). No significant effect of aminooxyacetic acid was observed on the serum nitrite levels in three episodes of hypoxic perconditioning in L-NAME-treated rats (Figure 6(b)).
Toxicity mechanism-based prodrugs: glutathione-dependent bioactivation as a strategy for anticancer prodrug design
Published in Expert Opinion on Drug Discovery, 2018
Xin-Yu Zhang, Adnan A. Elfarra
Once inside renal cells, DCVC can undergo further metabolism to be converted to reactive electrophiles [34], causing toxicity. Specifically, nephrotoxicity of DCVC has been attributed to two bioactivation pathways. In one pathway, DCVC undergoes a β-elimination reaction catalyzed by pyridoxal 5′-phosphate-dependent β-lyases to generate four reactive electrophiles: chlorothioketene (CTK), 2-chlorothionoacetyl chloride (2-CTA), and their corresponding hydrolysis products chloroketene (CK) and 2-chloroacetyl chloride (2-CA) [31,39]. Pretreatment of rats with aminooxyacetic acid (AOAA), a selective inhibitor of β-lyases, reduced nephrotoxicity of DCVC; S-(1,2-dichlorovinyl)-DL-α-methylcysteine, which cannot be cleaved by β-lyases, was not nephrotoxic [37,38,40,41], providing evidence for this pathway. The second pathway implicated in DCVC nephrotoxicity is the oxidation mediated by flavin-containing monooxygenase 3 (FMO3) [42–44], which leads to the formation of S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS; Figure 1), a highly reactive Michael acceptor [45]. In rats, the AOAA pretreatment did not protect against DCVCS nephrotoxicity but partly protected against DCVC nephrotoxicity [45], providing evidence for the in vivo presence of the two pathways.
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