Disease relevance of Roundup

• In vitro growth of Toxoplasma gondii, Plasmodium falciparum (malaria) and Cryptosporidium parvum was inhibited by the herbicide glyphosate, a well-characterized inhibitor of the shikimate pathway enzyme 5-enolpyruvyl shikimate 3-phosphate synthase [1].
• Toxicity of herbicide containing glyphosate [2].
• Roundup Ready plants carry the gene coding for a glyphosate-insensitive form of this enzyme, obtained from Agrobacterium sp. strain CP4 [3].
• A glyphosate-resistant aroA allele has been cloned in Escherichia coli from a mutagenized strain of Salmonella typhimurium [4].
• Solid-state NMR determination of glyphosate metabolism in a Pseudomonas sp [5].

Psychiatry related information on Roundup

• It was found that increases in heating temperature and heating time were unfavorable for the derivatization of glyphosate or glufosinate, whereas high temperature and extended reaction time remarkably facilitated that of AMPA and 3-MPPA except at 90 degrees C for an extended reaction time (120 min) [6].

High impact information on Roundup

• Glyphosate binds to the CP4 EPSP synthase in a condensed, noninhibitory conformation [3].
• Glyphosate sensitivity can be restored through a single-site mutation in the active site (Ala-100-Gly), allowing glyphosate to bind in its extended, inhibitory conformation [3].
• However, the following significant evolutionary constraint exists: in the absence of glyphosate, tolerant genotypes produced fewer seeds than susceptible genotypes [7].
• In the southeastern United States, weedy morning glories have begun to develop tolerance to glyphosate, representing a unique opportunity to examine the evolutionary genetics of a novel trait [7].
• We found genetic variation for tolerance, indicating the potential for the population to respond to selection by glyphosate [7].

Chemical compound and disease context of Roundup

• Solid-state NMR studies of regulation of N-(phosphonomethyl)glycine and glycine metabolism in Pseudomonas sp. strain PG2982 [8].
• The glyphosate-degrading bacterium, Burkholderia caryophilli PG2982, was observed to utilize glyceryl glyphosate as a sole phosphorus source [9].
• Degradation of glyphosate by Pseudomonas sp. PG2982 via a sarcosine intermediate [10].
• One of these changes, a proline to serine substitution at position 106 in the (R) biotype, corresponds to a substitution previously identified in a glyphosate-insensitive EPSPS enzyme from Salmonella typhimurium [11].
• 5-Enolpyruvylshikimate-3-phosphate synthase from Staphylococcus aureus is insensitive to glyphosate [12].

Biological context of Roundup

• Once incorporated into the plant genome, the gene product, CP4 EPSP synthase, confers crop resistance to glyphosate [3].
• Evidence for gene flow to 75 of 138 sentinel plants of A. stolonifera and to 29 of 69 resident Agrostis plants was based on seedling progeny survival after spraying with glyphosate in greenhouse assays and positive TraitChek, PCR, and sequencing results [13].
• The inactivation followed pseudo-first order kinetics, with a second order rate constant of 2.2 M-1 min-1 at pH 5.5 and 25 degrees C. The inactivation is prevented by preincubation of the enzyme with a combination of the substrate shikimate 3-phosphate plus glyphosate, but not by shikimate 3-phosphate, phosphoenolpyruvate, or glyphosate alone [14].
• The hydrolysis of glyceryl glyphosate to glyphosate by a phosphonate ester hydrolase (PEH) was identified as the first metabolic step in the mineralization pathway [9].
• The glyphosate-resistant phenotype is shown to be associated with the single amino acid substitution described above [4].

Anatomical context of Roundup

• Transcription of this gene is initiated at multiple sites in petunia leaves and in a glyphosate-tolerant petunia cell line overproducing EPSP synthase mRNA [15].
• Glyphosate-damaged anthers exhibited a change in the deposition of the secondary cell wall thickenings (SWT) in the endothecium cells, from the normal longitudinal orientation to a transverse orientation, and hindered septum disintegration [16].
• Plastid-expressed EPSPS could provide very high levels of glyphosate resistance, although levels of resistance in vegetative and reproductive tissues differed depending on EPSPS accumulation levels, and correlated to the plastid abundance in these tissues [17].
• Glyphosate-induced anther indehiscence in cotton is partially temperature dependent and involves cytoskeleton and secondary wall modifications and auxin accumulation [16].
• Our data demonstrate that glyphosate inhibits anther dehiscence by inducing changes in the microtubule and cell wall organization in the endothecium cells, which are mediated by auxin [16].

Associations of Roundup with other chemical compounds

• Glyphosate-based herbicides, such as Roundup, target the shikimate pathway enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, the functionality of which is absolutely required for the survival of plants [3].
• In the presence of shikimate 3-phosphate and glyphosate, only 1 of the 2 cysteines reacts with the reagent, with no loss of activity, suggesting that only 1 of these cysteines is at or near the active site of the enzyme [18].
• Incubation of 5-enolpyruvylshikimate-3-phosphate synthase, a target for the nonselective herbicide glyphosate (N-(phosphonomethyl)glycine), with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide in the presence of glycine ethyl ester resulted in a time-dependent loss of enzyme activity [14].
• The above results suggest that Glu-418 is the most accessible reactive carboxyl group under these conditions and is located at or close to the glyphosate binding site [14].
• In this study, the plastid-lethal markers, glyphosate or phosphinothricin herbicides, were used to develop a selection scheme for plastids that circumvents the need for integration of an antibiotic resistance marker [19].

Gene context of Roundup

• Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation [20].
• Overproduction by gene amplification of the multifunctional arom protein confers glyphosate tolerance to a plastid-free mutant of Euglena gracilis [21].
• Cloning of an Arabidopsis thaliana gene encoding 5-enolpyruvylshikimate-3-phosphate synthase: sequence analysis and manipulation to obtain glyphosate-tolerant plants [22].
• The efficiency of the glyphosate resistance marker for transformation and selection with plasmid pHR6/20-1 in S. cerevisiae laboratory strain SHY2 was found to be relatively high when compared with selection for LEU2 prototrophy [23].
• The glucose-6-phosphate dehydrogenase activity increased with all three treatments, but it decreased after glyphosate treatment, which does not stimulate the formation of peroxides [24].
• Only the concomitant mutations of Thr(97) and Pro(101) induce the conformational changes necessary to produce catalytically efficient, glyphosate-resistant class I EPSPS [25].

Analytical, diagnostic and therapeutic context of Roundup

• Selective overproduction of 5-enol-pyruvylshikimic acid 3-phosphate synthase in a plant cell culture which tolerates high doses of the herbicide glyphosate [26].
• Analyses by high-performance liquid chromatography and liquid scintillation spectrometry of the phloem sap collected from the castor bean system, used as a systemy test, indicate decreasing capacities of 2,4D, 2,4D-Lys, and glyphosate, respectively, to move from the epidermis cell wall to the sieve element [27].
• Thus, L'ELISA recognized the derivatized glyphosate more effectively (detection limit of 0.1 microg/L) and with increased sensitivity (10-100 times) over conventional ELISA and showed the potential for other applications [28].
• The correlation of L'ELISA and HPLC/MS for 66 surface water and groundwater samples was 0.97 with a slope of 1.28, with many detections of glyphosate and its degradate in surface water but not in groundwater [28].
• Capillary electrophoresis combined with mass spectrometry (CE-MS) was used for the rapid determination of the negatively charged herbicide, Glyphosate, in a selective dried granule (DG) formulation [29].

References