Organophosphates: Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.Diazinon: A cholinesterase inhibitor that is used as an organothiophosphorus insecticide.Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide.Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.Paraoxon: An organophosphate cholinesterase inhibitor that is used as a pesticide.Organophosphorus Compounds: Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.Organophosphate Poisoning: Poisoning due to exposure to ORGANOPHOSPHORUS COMPOUNDS, such as ORGANOPHOSPHATES; ORGANOTHIOPHOSPHATES; and ORGANOTHIOPHOSPHONATES.Parathion: A highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide.Organothiophosphorus Compounds: Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES.Tritolyl Phosphates: A mixture of isomeric tritolyl phosphates. Used in the sterilization of certain surgical instruments and in many industrial processes.Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (FUNGICIDES, INDUSTRIAL); INSECTICIDES; RODENTICIDES; etc.Insecticide Resistance: The development by insects of resistance to insecticides.Cholinesterase Reactivators: Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates.Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC An organochlorine insecticide whose use has been cancelled or suspended in the United States. It has been used to control locusts, tropical disease vectors, in termite control by direct soil injection, and non-food seed and plant treatment. (From HSDB)Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during WARFARE.Phosphoric Triester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the three ester bonds in a phosphotriester-containing compound.Pyrethrins: The active insecticidal constituent of CHRYSANTHEMUM CINERARIIFOLIUM flowers. Pyrethrin I is the pyretholone ester of chrysanthemummonocarboxylic acid and pyrethrin II is the pyretholone ester of chrysanthemumdicarboxylic acid monomethyl ester.Sarin: An organophosphorus ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent.CholinesterasesFenitrothion: An organothiophosphate cholinesterase inhibitor that is used as an insecticide.Carbamates: Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.Aryldialkylphosphatase: An enzyme which catalyzes the hydrolysis of an aryl-dialkyl phosphate to form dialkyl phosphate and an aryl alcohol. It can hydrolyze a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. It may also mediate an enzymatic protection of LOW DENSITY LIPOPROTEINS against oxidative modification and the consequent series of events leading to ATHEROMA formation. The enzyme was previously regarded to be identical with Arylesterase (EC A wide spectrum aliphatic organophosphate insecticide widely used for both domestic and commercial agricultural purposes.Butyrylcholinesterase: An aspect of cholinesterase (EC Inorganic salts or organic esters of phosphorous acid that contain the (3-)PO3 radical. (From Grant & Hackh's Chemical Dictionary, 5th ed)Neurotoxicity Syndromes: Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.Agricultural Workers' Diseases: Diseases in persons engaged in cultivating and tilling soil, growing plants, harvesting crops, raising livestock, or otherwise engaged in husbandry and farming. The diseases are not restricted to farmers in the sense of those who perform conventional farm chores: the heading applies also to those engaged in the individual activities named above, as in those only gathering harvest or in those only dusting crops.DEET: A compound used as a topical insect repellent that may cause irritation to eyes and mucous membranes, but not to the skin.Dichlorvos: An organophosphorus insecticide that inhibits ACETYLCHOLINESTERASE.Pralidoxime Compounds: Various salts of a quaternary ammonium oxime that reconstitute inactivated acetylcholinesterase, especially at the neuromuscular junction, and may cause neuromuscular blockade. They are used as antidotes to organophosphorus poisoning as chlorides, iodides, methanesulfonates (mesylates), or other salts.EsterasesIsoflurophate: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.Oximes: Compounds that contain the radical R2C=N.OH derived from condensation of ALDEHYDES or KETONES with HYDROXYLAMINE. Members of this group are CHOLINESTERASE REACTIVATORS.Agrochemicals: Chemicals used in agriculture. These include pesticides, fumigants, fertilizers, plant hormones, steroids, antibiotics, mycotoxins, etc.Pesticide Residues: Pesticides or their breakdown products remaining in the environment following their normal use or accidental contamination.Anopheles gambiae: A species of mosquito in the genus Anopheles and the principle vector of MALARIA in Africa.Receptors, Serotonin, 5-HT2: A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to the GQ-G11 G-PROTEINS resulting in increased intracellular levels of INOSITOL PHOSPHATES and free CALCIUM.Poisoning: A condition or physical state produced by the ingestion, injection, inhalation of or exposure to a deleterious agent.Antidotes: Agents counteracting or neutralizing the action of POISONS.Mevinphos: An organophosphate cholinesterase inhibitor that is used as an insecticide.Agriculture: The science, art or practice of cultivating soil, producing crops, and raising livestock.Temefos: An organothiophosphate insecticide.Carboxylic Ester Hydrolases: Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.Culex: A genus of mosquitoes (CULICIDAE) commonly found in tropical regions. Species of this genus are vectors for ST. LOUIS ENCEPHALITIS as well as many other diseases of man and domestic and wild animals.Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation.Mosquito Control: The reduction or regulation of the population of mosquitoes through chemical, biological, or other means.DDT: A polychlorinated pesticide that is resistant to destruction by light and oxidation. Its unusual stability has resulted in difficulties in residue removal from water, soil, and foodstuffs. This substance may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP-85-002, 1985). (From Merck Index, 11th ed)Carboxylesterase: Carboxylesterase is a serine-dependent esterase with wide substrate specificity. The enzyme is involved in the detoxification of XENOBIOTICS and the activation of ester and of amide PRODRUGS.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals.Environmental Monitoring: The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment (soil, air, and water), workplace, or in the bodies of people and animals present in that environment.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Animals, Newborn: Refers to animals in the period of time just after birth.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Kinetics: The rate dynamics in chemical or physical systems.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.

A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates. (1/724)

Azinphosmethyl (APM) is one of the most common insecticides used in fruit farming. The object of this paper is to develop a quick and practical test for assessing the risk for humans coming into contact with APM. It has been shown that the principal component of occupational and/or accidental exposure is through the skin (C. A. Franklin et al., 1981, J. Toxicol. Environ. Health 7, 715-731), but our approach is applicable to exposures via any route or a combination of routes. The method proposed in the present paper can accommodate a single-event exposure or repeated exposures over long periods. Urinary alkylphosphate (AP) metabolites are reliable bioindicators of the presence of APM in the body; they are easily accessible and can be used to estimate APM body burden. We developed a simple toxicokinetic model to link the time varying APM body burden to absorbed doses and to rates of elimination in the form of AP urinary metabolites. Using this model and data available in the literature, we are able to propose a "no observed adverse effect level" (NOAEL) for APM body levels and for corresponding absorbed doses. We have established that after a single exposure, the safe limit corresponding to the NOAEL is reached at a cumulative 0.215 mumoles AP/kg bw eliminated in urine in the first 24 hours following the beginning of exposure. For repeated daily exposures at steady state, the corresponding urinary AP metabolite level is equal to a cumulative 0.266 mumoles AP/kg bw eliminated per 24 hours.  (+info)

Mechanistic alternatives in phosphate monoester hydrolysis: what conclusions can be drawn from available experimental data? (2/724)

Phosphate monoester hydrolysis reactions in enzymes and solution are often discussed in terms of whether the reaction pathway is associative or dissociative. Although experimental results for solution reactions have usually been considered as evidence for the second alternative, a closer thermodynamic analysis of observed linear free energy relationships shows that experimental information is consistent with the associative, concerted and dissociative alternatives.  (+info)

EnvZ-independent phosphotransfer signaling pathway of the OmpR-mediated osmoregulatory expression of OmpC and OmpF in Escherichia coli. (3/724)

The Escherichia coli EnvZ-OmpR regulatory system is a paradigm of intracellular signal transduction mediated by the well-documented phosphotransfer mechanism, by which the expression of the major outer membrane proteins, OmpC and OmpF, is regulated in response to the medium osmolarity. Although it is clear that the EnvZ histidine(His)-kinase is the major player in the phosphorylation of OmpR, it has been assumed for some time that there may be an alternative phospho-donor(s) that can phosphorylate OmpR under certain in vitro and in vivo conditions. In this study, to address this long-standing issue, extensive genetic studies were done with certain mutant alleles, including delta envZ, delta(ackA-pta), and delta sixA, as well as delta ompR. Here, for the first time, genetic evidence is provided that, in addition to EnvZ, acetyl phosphate and an as yet unidentified sensor His-kinase can serve as alternative in vivo phospho-donors for OmpR, even in the envZ+ background. A model for the alternative phosphotransfer signaling pathway involved in the phosphorylation of OmpR is proposed.  (+info)

Vitamin B6 biosynthesis: formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein. (4/724)

In Escherichia coli the coenzyme pyridoxal 5'-phosphate (PLP) is synthesised de novo by a pathway that is thought to involve the condensation of 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose, catalysed by the enzymes PdxA and PdxJ, to form either pyridoxine (vitamin B6) or pyridoxine 5'-phosphate (PNP). Here we show that incubation of PdxJ with PdxA, 4-(phosphohydroxy)-L-threonine, NAD and 1-deoxy-D-xylulose-5-phosphate, but not 1-deoxy-D-xylulose, results in the formation of PNP. The PNP formed was characterised by (i) cochromatography with an authentic standard, (ii) conversion to pyridoxine by alkaline phosphatase treatment, and (iii) UV and fluorescence spectroscopy. Furthermore, when [2-(14)C]1-deoxy-D-xylulose-5-phosphate was used as a substrate, the radioactivity was incorporated into PNP. These results clarify the previously unknown role of PdxJ in the de novo PLP biosynthetic pathway. The sugar used as substrate by PdxJ is 1-deoxy-D-xylulose-5-phosphate rather than the previously assumed 1-deoxy-D-xylulose. The first vitamin B6 vitamer synthesised is PNP, and not pyridoxine.  (+info)

Conservation of nitrogen in cattle feedlot waste with urease inhibitors. (5/724)

Feedlot cattle normally retain less than 20% of their dietary nitrogen intake. Sixty to 80% of the nitrogen excreted is normally lost through volatilization of ammonia, which is primarily generated from urea. This loss of ammonia nitrogen pollutes the environment and creates an unfavorable ratio of nitrogen to phosphorous (N:P) in the waste for crop growth. Two urease inhibitors, cyclohexylphosphoric triamide (CHPT) and N-(n-butyl) thiophosphoric triamide (NBPT) were evaluated for their ability to reduce the rate of urea hydrolysis in beef cattle feedlot pens. Initially, a total of six pens were used, two pens per treatment, with approximately 70 cattle per pen, and a single topical application of CHPT or NBPT at 20 mg/kg of manure. Essentially no urea was found in untreated pens. However, with CHPT treatment, 2 g of urea/kg of dry manure accumulated by d 4, and all gradually disappeared by d 11; NBPT conserved 3 and 3.5 g of urea/kg by d 4 and 9, respectively, and it had disappeared by d 14 (treatment [trt] x day, P = .003). A second study involved application of NBPT weekly for 6 wk. This caused urea to accumulate to a peak concentration of 17 g/kg of manure by d 30 (trt x day2, P = .001). Once the treatment was stopped the urea concentration began to decrease. When the NBPT was applied weekly, the concentration of ammonia in the waste was less for the treated pens (trt x day, P = .01), the total nitrogen was greater (trt x day, P = .04), pH tended to be lower (trt x day, P = .10), and the total volatile acids were not different (trt x day, P = .51) from untreated pens. We concluded that urease inhibitors could be used to control ammonia emissions from animal wastes, prevent environmental damage, and produce a more balanced (N:P) fertilizer from manure.  (+info)

Calcium dependence of Pi phosphorylation of sarcoplasmic reticulum Ca2+-ATPase at low water content: water dependence of the E2-->E1 conversion. (6/724)

Enzymes entrapped in reverse micelles can be studied in low-water environments that have the potential of restricting conformational mobility in specific steps of the reaction cycle. Sarcoplasmic reticulum Ca2+-ATPase was incorporated into a reverse-micelle system (TPT) composed of toluene, phospholipids, Triton X-100 and varying amounts of water (0.5-7%, v/v). Phosphorylation of the Ca2+-ATPase by ATP required the presence of both water and Ca2+ in the micelles. No phosphoenzyme (EP) was detected in the presence of EGTA. Phosphorylation by Pi (inorganic phosphate) in the absence of Ca2+ was observed at water content below that necessary for phosphorylation by ATP. In contrast to what is observed in a totally aqueous medium, EP formed by Pi was partially resistant to dephosphorylation by Ca2+. However, the addition of non-radioactive Pi to the EP already formed caused a rapid decrease in radiolabelled enzymes, as expected for the isotopic dilution, indicating the existence of an equilibrium (E+Pi<-->EP). Phosphorylation by Pi also occurred in TPT containing millimolar Ca2+ concentrations in a range of water concentrations (2-5% v/v). The substrates p-nitrophenyl phosphate, acetyl phosphate, ATP and GTP increased the EP level under these conditions. These results suggest that: (1) the rate of conversion of the ATPase conformer E2 into E1 is greatly reduced at low water content, so that E2-->E1 becomes the rate-limiting step of the catalytic cycle; and (2) in media of low water content, Pi can phosphorylate both E1Ca and E2. Thus, the effect of enzyme hydration is complex and involves changes in the phosphorylation reaction at the catalytic site, in the equilibrium between E2 and E1 conformers, and in their specificity for substrates.  (+info)

Formation of adenosine 5'-tetraphosphate from the acyl phosphate intermediate: a difference between the MurC and MurD synthetases of Escherichia coli. (7/724)

The mechanism of the Mur synthetases of peptidoglycan biosynthesis is thought to involve in each case the successive formation of an acyl phosphate and a tetrahedral intermediate. The existence of the acyl phosphates for the MurC and MurD enzymes from Escherichia coli was firmly established by their in situ reduction by sodium borohydride followed by acid hydrolysis, yielding the corresponding amino alcohols. Furthermore, it was found that MurD, but not MurC, catalyses the synthesis of adenosine 5'-tetraphosphate from the acyl phosphate, thereby substantiating its existence and pointing out a difference between the two enzymes.  (+info)

Stimulated activity of human topoisomerases IIalpha and IIbeta on RNA-containing substrates. (8/724)

Eukaryotic topoisomerase II is a dimeric nuclear enzyme essential for DNA metabolism and chromosome dynamics. Central to the activities of the enzyme is its ability to introduce transient double-stranded breaks in the DNA helix, where the two subunits of the enzyme become covalently attached to the generated 5'-ends through phosphotyrosine linkages. Here, we demonstrate that human topoisomerases IIalpha and IIbeta are able to cleave ribonucleotide-containing substrates. With suicide substrates, which are partially double-stranded molecules containing a 5'-recessed strand, cleavage of both strands was stimulated approximately 8-fold when a ribonucleotide rather than a deoxyribonucleotide was present at the scissile phosphodiester of the recessed strand. The existence of a ribonucleotide at the same position in a normal duplex substrate also enhanced topoisomerase II-mediated cleavage, although to a lesser extent. The enzyme covalently linked to the 5'-ribonucleotide in the cleavage complex efficiently performed ligation, and ligation occurred equally well to acceptor molecules terminated by either a 3'-ribo- or deoxyribonucleotide. Besides the enhanced topoisomerase II-mediated cleavage of ribonucleotide-containing substrates, cleavage of such substrates could be further stimulated by ATP or antitumor drugs. In conclusion, the observed in vitro activities of the human topoisomerase II isoforms indicate that the enzymes can operate on RNA or RNA-containing substrates and thus might possess an intrinsic RNA topoisomerase activity, as has previously been demonstrated for Escherichia coli topoisomerase III.  (+info)

  • This represents a novel approach in biomarker analysis because exposure to each different organophosphate (OP) chemical nerve agent results in a distinct protein "fingerprint" structure that can be identified, distinguished from other agents, and quantified. (
  • The broad objective of this proposal is to develop an extremely sensitive and selective biosensor device capable of detecting and discriminating proteins in human serum samples taken from personnel that have been exposed to potentially harmful levels of organophosphate-based nerve gas. (
  • Long-term change in feeding behavior was produced by organophosphate insufficient to induce outward illness or to depress brain AChE activity. (
  • AChE insensitive to organophosphate chemotherapeutants has been identified as a major resistance mechanism in numerous arthropod species, and in this study, target-site resistance was confirmed in the crustacean Lepeophtheirus salmonis Krøyer isolated from several fish-farming areas in Norway and Canada. (
  • Due to their toxicity, persistence, and adverse effects, some organophosphates (like parathion and methyl parathion) were classified and registered as extremely hazardous by the World Health Organization (WHO) and US EPA (US Environmental Protection agency) and have been banned in many countries. (
  • The three major types of PTE are reported so far, such as organophosphate hydrolase (OPH), methyl parathion hydrolase (MPH), and organophosphorus acid anhydrolase (OPAA) encoded by opd , mpd , and opaA genes, which are either located on plasmid or on chromosomal DNA. (
  • Organophosphates (OPs) are chemical substances originally produced by the reaction of alcohols and phosphoric acid. (
  • The organophosphates octamethyl pyrophosphoramide, Bidrin, and phosphoric acid 2,2-dichlorovinyl dimethyl ester inhibit the membrane voltage response of frog sartorius muscles to carbamylcholine in a manner expected of either a slowly reversing competitive inhibitor or a noncompetitive inhibitor. (
  • Organophosphate pesticides (OPPs), like some nerve agents, inhibit this neuromuscular enzyme, which is broadly essential for normal function in insects, but also in humans and many other animals. (
  • Dr Cherry in comments, said: "The study was set up to test a clear hypothesis, that those whose genes produced a less efficient enzyme would, if exposed to organophosphates, be more likely to become ill. (
  • Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. (
  • A potentiometric enzyme electrode for the direct measurement of organophosphate (OP) nerve agents was developed. (
  • Combining p-methyl DL and NWH with LLINs could provide significant epidemiological benefits against a vector population which is resistant to pyrethroids but susceptible to organophosphates. (
  • The 56 year old male patient ingested an unknown dose of the organophosphate demeton-S-methyl-sulphone (Metasystox R) in a suicide attempt. (
  • As long ago as 1951, the 1951 Zuckerman Report's scientific findings had drawn links between organophosphates and the nerve agents used in chemical weapons. (
  • the EPA banned most residential uses of organophosphates in 2001, but their agricultural use, as pesticides on fruits and vegetables, is still permitted, and they are as is their use in mosquito abatement in public spaces such as parks. (
  • Dieter, M. P., and J. L. Ludke: Studies on combined effects of organophosphates and heavy metals in birds. (
  • The results caution against using median lethal dietary concentrations for other than ranking chemicals based on their relative toxicity, particularly in establishing safe environmental levels, and suggest that anorexia and physiological condition may be important factors in mortality of wild birds exposed to organophosphates. (
  • The United States Environmental Protection Agency lists organophosphates as very highly acutely toxic to bees, wildlife, and humans. (
  • Prevention includes banning very toxic types of organophosphates. (
  • Researchers calculated the odds ratios for polymorphisms in the gene regulating paraoxonase, and therefore the ability to break down toxic organophosphates. (
  • It is thought that worldwide, approximately 3 million people are exposed to toxic levels of organophosphates, including approximately 2 million hospitalisations for suicidal ingestion 1 . (