Toxicovigilance: New biochemical tool used in sulfonylurea herbicides toxicology studies (original) (raw)
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commercial herbicide Oust , is a potent and selective inhibitor of acetolactate synthase (ALS) (E.C. 4.1.3.18) in various bacteria (1,2), yeast (3), and plants (4,5). ALS is the first common enzyme in the biosynthesis of the branched-chain amino acids. This enzyme has an absolute requirement for FAD (1,6,7) although an ALS involved in the biosynthesis of acetoin from Aerobacter aerogenes does not require FAD (8). Since the reaction catalyzed by ALS involves no net redox, the requirement for FAD is unusual. Spectral changes in ALS-bound FAD
The Journal of biological chemistry, 1984
The sulfonylurea herbicide sulfometuron methyl inhibits the growth of several bacterial species. In the presence of L-valine, sulfometuron methyl inhibits Salmonella typhimurium, this inhibition can be reversed by L-isoleucine. Reversal of growth retardation by L-isoleucine, accumulation of guanosine 5'-diphosphate 3'-diphosphate (magic spot), and relA mutant hypersensitivity suggest sulfometuron methyl interference with branched-chain amino acid biosynthesis. Growth inhibition of S. typhimurium is mediated by sulfometuron methyl's inhibition of acetolactate synthase, the first common enzyme in the branched-chain amino acid biosynthetic pathway. Sulfometuron methyl exhibits slow-binding inhibition of acetolactate synthase isozyme II from S. typhimurium with an initial Ki of 660 +/- 60 nM and a final, steady-state Ki of 65 +/- 25 nM. Inhibition of acetolactate synthase by sulfometuron methyl is substantially more rapid (10 times) in the presence of pyruvate with a maximal...
Inhibition of Sulfotransferases by Xenobiotics
Current Drug Metabolism, 2006
The sulfotransferase (SULT) family comprises important phase II conjugation enzymes for the detoxification of xenobiotics and modulation of the activity of physiologically important endobiotics such as thyroid hormones, steroids, and neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group, donated by 3′-phosphoadenosine-5′phosphosulfate (PAPS), to an acceptor substrate that may be a hydroxy group or an amine group in a process originally called sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT activity may be inhibited when humans are exposed to certain xenobiotics including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.), dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls, hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse effects on human health. For example, hydroxylated polychlorinated biphenyls have been shown to interfere with the transport of thyroid hormones, inhibit estradiol sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic xenobiotics usually decreases their toxicity, so inhibition of this pathway may lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates are chemically reactive, inhibition of their formation may protect from toxicity. This manuscript will review the literature concerning the inhibition of SULTs by xenobiotics including isoform-selective effects, inhibition kinetics and health effects resulting from the inhibition.
Elucidating the Specificity of Binding of Sulfonylurea Herbicides to Acetohydroxyacid Synthase
Biochemistry, 2005
Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is the target for the sulfonylurea herbicides, which act as potent inhibitors of the enzyme. Chlorsulfuron (marketed as Glean) and sulfometuron methyl (marketed as Oust) are two commercially important members of this family of herbicides. Here we report crystal structures of yeast AHAS in complex with chlorsulfuron (at a resolution of 2.19 Å), sulfometuron methyl (2.34 Å), and two other sulfonylureas, metsulfuron methyl (2.29 Å) and tribenuron methyl (2.58 Å). The structures observed suggest why these inhibitors have different potencies and provide clues about the differential effects of mutations in the active site tunnel on various inhibitors. In all of the structures, the thiamin diphosphate cofactor is fragmented, possibly as the result of inhibitor binding. In addition to thiamin diphosphate, AHAS requires FAD for activity. Recently, it has been reported that reduction of FAD can occur as a minor side reaction due to reaction with the carbanion/enamine of the hydroxyethyl-ThDP intermediate that is formed midway through the catalytic cycle. Here we report that the isoalloxazine ring has a bent conformation that would account for its ability to accept electrons from the hydroxyethyl intermediate. Most sequence and mutation data suggest that yeast AHAS is a high-quality model for the plant enzyme.
Archives of Microbiology, 1991
The sulfonylurea herbicides exert their effects on cells via their inhibition of the acetohydroxy acid synthase (AHS) enzymes. Although chlorsulfuron and sulfometuron methyl often affected microbial growth differently their effects on the AHS activities of toluenised cells were similar. Sulfometuron methyl was always a more potent inhibitor than chlorsulfuron. We have postulated that sulfometuron methyl penetrated into microbial cells more readily then did chlorsulfuron. The effect of the herbicides on microbial growth was altered by the composition of the medium and in particular by valine or valine plus isoleucine. Different microorganisms had different complements of AHS isoenzymes which together with differences in permeability were the most likely explanations for the different responses observed. It was pointed out that application of these sulfonylurea herbicides would have significant effects on the microbial ecological balance of soil, and particularly so in alkaline soils. The consequences would be most evident in agricultural situations where the microbial population played an important role in maximising the productivity of crops.
Fundamental Toxicological Sciences
2019
Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl)butane] is an isothiocyanate derivative from cruciferous vegetables, with anti-proliferative actions on various cancer and tumor cells. In this paper, we envisaged the effects of sulforaphane on various functions (growth inhibition, cytotoxicity and enhancement of O2-generating activity) of human monoblastic leukemia U937 cells. Sulforaphane showed strong cytotoxicity, resulting in inhibition of proliferation in a dose-dependent manner. In addition, cell differentiation induced by 1 μM all-trans retionic acid (RA) remarkably caused the enhanced resistance against cytotoxicity of sulforaphane. Moreover, the RA-induced O2-generating activity was also enhanced by sulforaphane in a dose dependent manner. When U937 cells were cultured in the presence of 1 μM RA and 2 μM sulforaphane, the O2-generating activity increased more than 2.5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment wit...
Hydrolysis of sulfonylurea herbicides in soils and aqueous solutions: a review
Journal of agricultural and food …, 2002
Sulfonylureas are a unique group of herbicides used for controlling a range of weeds and some grasses in a variety of crops and vegetables. They have been extremely popular worldwide because of their low mammalian toxicity, low use rate, and unprecedented herbicidal activity. Knowledge about the fate and behavior of sulfonylurea herbicides in the soil-water environment appears to be of utmost importance for agronomic systems and environmental protection. Because these herbicides are applied at a very low rate, and their mobility is greatly affected by the chemicals' anionic nature in alkaline soils, a thorough understanding of their degradation/hydrolysis processes and mechanisms under aqueous and soil systems is important. This review brings together published information on the hydrolysis of several sulfonylureas in aqueous and soil solutions that includes the effects of pH, temperature, functional relationship between pH vs hydrolysis rate constants, and hydrolysis behavior of sulfonylureas in the presence of minerals. In addition, the transformations of sulfonylureas in soil, under laboratory and field experiments, have been discussed in connection with the compounds' varied structural features, i.e., sulfonylueas that are with or without the pyridinic, pyrimidine, and triazinic ring.
Carcinogenesis, 2002
Glucoraphanin in Brassica vegetables breaks down to either sulforaphane or sulforaphane nitrile depending on the conditions, and sulforaphane can be further conjugated with glutathione. Using a high-throughput microtitre plate assay and TaqMan real time quantitative RT-PCR to measure mRNA, we show that sulforaphane and its glutathione conjugate, but not the nitrile, increased significantly (P < 0.05) both UGT1A1 and GSTA1 mRNA levels in HepG2 and HT29 cells. These changes were accompanied by an increase in UGT1A1 protein, as assessed by immunoblotting, and a 2-8-fold increase in bilirubin glucuronidation. When treated together, the nitrile derivative did not affect sulforaphane induction. The induction of UGT1A1 and GSTA1 mRNA by sulforaphane was time and concentration dependent. The results show a functional induction of glucuronidation by sulforaphane but not sulforaphane nitrile, and show that the pathway of metabolism of glucosinolates in Brassica vegetables is important in determining the resulting biological and anticarcinogenic activities.