DFP diisopropyl

Diethylenetriaminepentaacetic acid DFMO al-Difluoromethyl ornithine DFP Diisopropyl fluorophosphate DFX Desferrioxamine DGLA Dihomo-y-linolenic acid DH Delayed hypersensitivity DHA Docosahexaenoic acid DHBA Dihydroxybenzoic acid DHR Delayed hypersensitivity reaction... 

The mechanism by which A-esterases hydrolyze organophosphates is not completely understood. Involvement of a phosphorylated active-site cysteine and displacement of an activated H20 molecule are two possible hypotheses (see Sect. 3.7.1) [56], A-Esterases comprise enzymes that hydrolyze aryl esters, paraoxon (2.2) and related organophosphate pesticides, and diisopropyl-fluorophosphate (DFP, diisopropyl phosphorofluoridate, 2.3) and related compounds, including nerve gases. These enzymes are found in the current nomenclature listed under arylesterases, aryldialkylphosphatase, and diisop-ropyl-fluorophosphatase. 

Little is yet known in regard to factors that might cause individual variation in acetylcholinesterase activity. The activity is greatly reduced in erythrocytes of persons with paroxysmal nocturnal hemoglobinuria, but this condition is rare (42). It has been reported that extended inhibition by organophosphates does not appear to affect adversely the survival of erythrocytes in the circulation as evidenced by observations (28,60,92) with DFP (diisopropyl fluorophosphonate), OMPA (octa-methyl pyrophosphoramide), and malathion (O,O-dimethyl dithiophos-phate of diethyl mercaptosuccinate). 

DFP diisopropyl fluorophosphate DNA deoxyribonucleic acid DNFB dinitrofluorobenzene DNP dinitrophenol... 

Insecticides and nerve gases act as irreversible inhibitors of acetylcholinesterase, an enzyme needed for nerve conduction. The compound DFP (diisopropyl fluorophosphate), an organophosphate insecticide, forms a covalent bond with the side chain —CH2OH of serine in the active site. When acetylcholinesterase is inhibited, the transmission of nerve impulses is blocked, and paralysis occurs. 

The esters of monofluorophosphoric acid are of great interest because of their cholinesterase inhibiting activity which causes them to be highly toxic nerve gases and also gives them medical activity (see Enzyme inhibitors). The most studied is the bis(l-methylethyl)ester of phosphorofluoridic acid also known as diisopropyl phosphorofluoridate [155-91 DFP (5), and as the ophthalmic ointment or solution Isoflurophate USP. It is used as a... 

Inhibitors which interact only with peptidases of one catalytic type include pepstatin (aspartic peptidases) E64 (cysteine peptidases from clan CA) diisopropyl fluorophosphates (DFP) and phenylmethane sulfonyl-fluoride (PMSF) (serine peptidases). Bestatin is a useful inhibitor of aminopeptidases. 

A few OP compounds cause delayed neuropathy in vertebrates because they inhibit another esterase located in the nervous system, which has been termed neuropathy target esterase (NTE). This enzyme is described in Chapter 10, Section 10.2.4. OPs that cause delayed neuropathy include diisopropyl phosphofluoridate (DFP), mipafox, leptophos, methamidophos, and triorthocresol phosphate. The delay in the appearance of neurotoxic symptoms following exposure is associated with the aging process. In most cases, nerve degeneration is not seen with initial inhibition of the esterase but appears some 2-3 weeks after commencement of exposure, as the inhibited enzyme undergoes aging (see Section 16.4.1). The condition is described as OP-induced delayed neuropathy (OPIDN). 

Van Voris P, Cataldo DA, Ligotke MW, et al. 1987. Acute environmental toxicity and persistence of selected chemical agent simulants diisopropyl flourophosphate (DFP) and diisopropyl methylphosphonate (DIMP). NTIS No. AD-A181-309. 

Organophosphorus esters are known to react with a serine hydroxyl group in the active site of the acetylcholinesterase protein (Ecobichon 1991 Murphy 1986). Some organophosphorus esters (e.g., diisopropyl fluorophosphate, [DFP]) bind irreversibly, while others bind in a slowly reversible fashion, thereby leading to a slow reactivation (dephosphorylation) of the enzyme. A process known as "aging" has also been described in which reversibly bound compounds are changed with time to moieties that are essentially irreversibly... 

Most poly(HA) depolymerases are inhibited by reducing agents, e.g., dithio-erythritol (DTT), which indicates the presence of essential disulfide bonds, and by serine hydrolase inhibitors such as diisopropyl-fluoryl phosphate (DFP) or acylsulfonyl derivates. The latter compounds covalently bind to the active site serine of serine hydrolases and irreversibly inhibit enzyme activity [48]. 

Diisopropyl fluorophosphate (DFP DYFLOS) Hexaethyl tetraphosphate (HETP) 0.025% topical (eye)... 

Mazur and Bodansky (1946) found that diisopropyl fluorophosphate (DFP) irreversibly inhibits acetylcholine esterase. In particular, in 1949 Jansen, Balls, and their collaborators demonstrated the stoichiometric reaction of DFP with chymotrypsin (Jansen et al., 1949a,b Aldridge, 1950). 

The uPAR protein was initially purified from lysates of phorbol ester-stimulated U937 cells by affinity chromatography using diisopropyl fluoro-phosphates (DFP)-inactivated uPA [53, 54]. uPAR is anchored in the plasma membrane by a glycosylphosphatidylinositol (GPI) moiety and it consists of 283 amino acids in its processed form [55, 56]. The protein is composed of three domains and each domain contains 90 amino acids. The domains are connected by linker regions with a length of 15-20 amino acids [57, 58]. The disulfide bonds in the N-terminal domain I have been experimentally determined and the pattern of cysteine residues in the sequence has revealed... 

The nerve gas diisopropyl fluorophosphate (DFP) reacts with the serine —OH in some enzymes to form HF and the (9-phosphoryl ester as follows ... 

Groh, D., Harvey, A.M., Langworthy, O.R., Lilenthal, J.L. (1947). The administration of diisopropyl fluorophosphate (DFP) to man. III. Effects on the central nervous system with special reference to the electrical activity of the brain. Bull. Johns Hopkins Hasp. 81 257. 

FIGURE 42.6. Levels of high-energy phosphates, ATP (A) and PCr (B) in amygdala and hippocampus of rats intoxicated with an acute dose of carhofuran (CF, 1.25mg/kg, s.c.) or diisopropyl phosphorofluoridate (DFP, 1.25mg/kg, s.c.). Rats were sacrificed 1 hour (1 h) or 3 days (3 d) after CF or DFP injection. Values of ATP and PCr are presented as means SEM (n = 4-6). Significant difference between values from control rats and DFP- or CF-treated rats (p < 0.05). 

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