China
Africa
Explore chapters and articles related to this topic
Role of Metabolism in Chemically Induced Nephrotoxicity
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
The critical step in the bioactivation process, metabolism of the cysteine S-conjugate by the β-lyase, has been demonstrated in vivo and in numerous in vitro experimental systems with the PLP enzyme inhibitor aminooxy acetic acid (AOAA): inhibition of the β-lyase with AOAA prevents the toxicity of several haloalkyl and haloalkenyl cysteine S-conjugates (Boogaard et al., 1989; Chen et al., 1990a; Dohn et al., 1985b; Elfarra and Anders, 1984; Elfarra et al., 1986a; Lash and Anders, 1986, 1987; Lash et al., 1986b, 1990a; Stevens et al., 1986, 1988, 1989; Wallin et al., 1987; Wolfgang et al., 1989). Conversely, stimulation of the β-lyase activity with exogenous 2-keto acids potentiates DCVC-induced toxicity in isolated rat kidney cells and in isolated renal mitochondria (Elfarra et al., 1987). 2-Keto acids play an important role in modulation of β-lyase activity (see below).
Metabolism of Glutamate and Glutamine in Neurons and Astrocytes in Primary Cultures
Published in Elling Kvamme, Glutamine and Glutamate in Mammals, 1988
Pathways which potentially could be involved in either conversion of glutamate to other compounds or in formation of glutamate from its precursors are illustrated in Figure 1. Glutamate can be converted to GABA (a process occurring only in GABAergic neurons), glutamine, or α-ketoglutarate (2-oxoglutarate), a tricarboxylic acid (TCA) cycle constituent. The latter process can occur either as a transamination, catalyzed by aspartate aminotransferase (AAT) (Chapter 8, Volume I), or as an oxidative deamination, catalyzed by glutamate dehydrogenase (GLDH) (Chapter 6, Volume I). A distinction between these possibilities can be achieved by the use of aminooxy acetic acid (AO A A), an inhibitor of the transamination but not of the oxidative deamination. The formation of glutamine, which requires ATP, is catalyzed by glutamine synthetase (GS) (Chapter 2, Volume I), and that of GABA is catalyzed by glutamate decarboxylase (GAD) (Chapter 7, Volume I).
Glutamate Decarboxylase
Published in Elling Kvamme, Glutamine and Glutamate in Mammals, 1988
Jang-Yen Wu, Larry A. Denner, Chin-Tarng Lin, Bang Hwang
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.
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
The synthesis of CREKA and SREKA homing peptides was carried out by SPPS using Fmoc/tBu strategy on Fmoc-Rink-amide-MBHA resin as solid support. In the final step, isopropylidene-protected aminooxyacetic acid (> =Aoa-OH) was attached to the N-terminus of the SREKA peptide for the development of oxime linkage (Supplementary Scheme S1). In the case of the aminooxyacetyl-functionalized SREKA, the peptide derivative cleaved from the resin was purified by RP-HPLC followed by the removal of the isopropylidene protection (Aoa-SREKA-NH2). The salts and side products were separated by RP-HPLC before the conjugation of the functionalized peptide to the fatty acid derivative. As a control, a Cys containing homing peptide (H-CREKA-NH2) was also investigated for the coupling to the maleimide-functionalized DSPE-PEG phospholipid analog. The peptides were characterized by analytical RP-HPLC and mass spectrometry (Supplementary Figures S1 and S2).
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)).