Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Sonication of bovine liver microsomes completely solubilized the membrane-bound lysophospholipase II (EC 3.1.1.5). Co-chromatography with purified 125I-labelled lysophospholipase indicated that the enzyme was solubilized from microsomes in a lipid-free state. 2. In the presence of residual microsomal membranes, the solubilized lysophospholipase could only be partly degraded by trypsin (EC 3.4.21.4). Therefore, trypsin could not be used to study the transmembrane disposition of lysophospholipase in intact microsomes. 3. Chymotrypsin (EC 3.4.21.1) destroyed the solubilized lysophospholipase activity, even in the presence of residual microsomal membranes. 4. Lysophospholipase in intact microsomal vesicles was resistant to chymotrypsin digestion. 5. When microsomal vesicles were made leaky with lysophosphatidylcholine, chymotrypsin destroyed more than 95% of the lysophospholipase activity. 6. It is concluded from these experiments that at least the active center of lysophospholipase is located at the luminal side of the bovine liver microsomal membrane.
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PMID:Studies on the transverse localization of lysophospholipase in bovine liver microsomes using proteolytic enzymes. 45 32

The fate of palmitoyl-lysophosphatidylcholine (lysoPC) incorporated into the membrane of intact human erythrocytes from a medium was investigated under nonhemolytic conditions at 37 degrees C by means of 14C-labeled tracers. The lysoPC was first incorporated into the outer half of the membrane lipid bilayer and then gradually translocated into the inner half during the incubation. At the same time it was metabolically converted into phosphatidylcholine (PC) and free fatty acid (FFA) plus glycerophosphorylcholine by the actions of acyltransferase and lysophospholipase, respectively. The half times of the conversion were about 14 h, while the value of 0.5 h was obtained when the half time was measured with the hemolysate of the lysoPC-loaded erythrocytes. Chymotrypsin treatment of unsealed ghosts caused a definite decrease in lysophospholipase activity, while similar treatment of resealed ghosts did not. This together with other evidence already reported in the literature suggests that both lysophospholipase and acyltransferase may be located in the inner surface of the membrane. The above findings strongly suggest that the most of the lysoPC loaded to the membrane is gradually translocated from the outer to the inner half of the bilayer and soon converted to either PC or FFA.
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PMID:Quantitative studies on translocation and metabolic conversion of lysophosphatidylcholine incorporated into the membrane of intact human erythrocytes from the medium. 399 95

2-Substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides (2-substituted-BDPOs) are of special interest as neuropathy target esterase (NTE) inhibitors because they include not only the neuropathic metabolite of tri-o-cresyl phosphate (the 2-methylphenoxy analog) but also the most potent NTE inhibitors known. These compounds react much faster with NTE than 2 standard inhibitors, O,O-diisopropyl fluorophosphonate (DFP) and mipafox. alpha-Chymotrypsin is similar to NTE in undergoing rapid inhibition by BDPOs which is known to involve phosphorylation followed by aging. NTE and alpha-chymotrypsin were compared for reaction rates with BDPOs varying in the 2-substituent as follows: 4-methyl-, 4-propyl-, and 4-hexylphenoxy; butyl, octyl and dodecyl; (S)- and (R)-butyl. The active site of NTE differs from that of alpha-chymotrypsin in preference for long-chain substituents and in stereospecificity.
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PMID:Reactivity and stereospecificity of neuropathy target esterase and alpha-chymotrypsin with 2-substituted-4H-1,3,2-benzodioxaphosphorin 2-oxides. 794 May 98

Organophosphorus pesticide toxicology is normally evaluated in relation to inhibition of cholinesterases (acetyl and butyryl), neuropathy target esterase, and carboxylesterases, with less attention given to other physiologically important hydrolases. This study considers the relative organophosphate sensitivities of the aforementioned serine hydrolases compared with purified blood-clotting factors (thrombin, plasmin, and kallikrein) and digestive enzymes (alpha-chymotrypsin, trypsin, and elastase), assayed under similar conditions. Inhibitors that we examined are organophosphorus insecticides or their activated metabolites (paraoxon, chlorpyrifos oxon, and profenofos) and other toxicants (phenyl saligenin cyclic phosphonate and tribufos) for comparison with values that are found in the literature for the fluorophosphonates (isoflurophate and sarin). Thrombin is the most sensitive blood-clotting factor with IC-50 values of 19 to 160 microM for tribufos, the cyclic phosphonate, isoflurophate, and profenofos; plasmin and kallikrein are less affected (IC-50 >100 microM). Alpha-Chymotrypsin, trypsin, and elastase are most sensitive to the cyclic phosphonate (IC-50 1.3-15 microM) and less so to isoflurophate, sarin, and profenofos (IC-50 values from 3.6 to greater than 100 microM). The cholinesterases, carboxylesterase, and neuropathy target esterase are the most sensitive to inhibition with IC-50 values for the insecticides of less than 0.001 to 0.6, 0.002 to 0.009, and 0.15 to 100 microM, respectively. The generally low potency of these organophosphates for blood-clotting factors and digestive enzymes suggests that associated toxic effects are unlikely at sublethal doses.
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PMID:Sensitivity of blood-clotting factors and digestive enzymes to inhibition by organophosphorus pesticides. 1056 Oct 82