Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two forms of clathrin light chains (LCA and LCB) or clathrin-associated proteins (CAP1 and CAP2) have presented an immunochemical paradox. Biochemically similar, both possess two known functional parameters: binding the clathrin heavy chain and mediating the action of an uncoating ATPase. All previously reported anti-CAP mAbs, however, react specifically with only CAP1 (Brodsky, F. M., 1985, J. Cell Biol., 101:2047-2054; Kirchhausen, T., S. C. Harrison, P. Parham, and F. M. Brodsky, 1983, Proc. Natl. Acad. Sci. USA, 80:2481-2485). Four new anti-CAP mAbs are reported here: two, C-7H12 and C-6C1, react with both forms; two others, C-10B2 and C-4E5, react only with the lower form. Sandwich ELISAs indicated that C-10B2, C-4E5, C-6C1, and C-7H12 react with distinct epitopes. Monoclonal antibodies C-10B2 and C-4E5 immunoprecipitate clathrin-coated vesicles (CCVs) and react with CAP2 epitopes accessible to chymotrypsin on the vesicle. These mAbs inhibit phosphorylation of CAP2 by endogenous CCV casein kinase II. In contrast, C-6C1 and C-7H12 react with epitopes that are relatively insensitive to chymotrypsin. CAP peptide fragments containing these epitopes remain bound to reassembled cages or CCVs after digestion. Immunoprecipitation and ELISAs demonstrate that C-7H12 and C-6C1 react with unbound CAPs but not with CAPs bound to triskelions or CCVs. The data indicate that the CAPs consist of at least two discernible structural domains: a nonconserved, accessible domain that is relevant to the phosphorylation of CAP2 and a conserved, inaccessible domain that mediates the binding of CAPs to CCVs.
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PMID:Mapping two functional domains of clathrin light chains with monoclonal antibodies. 243 41

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.
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PMID:The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis. 337 92

Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to alpha 1-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 micrograms/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 micrograms/L. Also, 25% of all men with benign prostate hyperplasia (BPH) have serum PSA levels above 4 micrograms/L. Using assays specially developed to measure free and complexed forms of PSA in serum, we found the proportion of PSA-ACT complexes to be higher in CAP than in BPH, but the ratio of free-to-total PSA in serum to be lower. Using an abnormally low ratio of free-to-total PSA to detect CAP increases diagnostic specificity by 15 to 20%, compared to using a high serum PSA concentration. This suggests that the ratios of free-to-total PSA significantly increase the ability to distinguish BPH from localized CAP. The molecular basis is unclear, but may be related to the high incidence of prostate tumor cells producing both PSA and ACT. This is in contrast to the lack of ACT production in BPH epithelium. Possibly owing to lack of ACT production in BPH areas, conditions are not optimal for complex formation, whereas tumors producing both ACT and PSA may promote the formation of PSA-ACT complexes in CAP.
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PMID:Regulation of the enzymatic activity of prostate-specific antigen and its reactions with extracellular protease inhibitors in prostate cancer. 754 78

Previously reported allergic reactions to orgotein (superoxide dismutase) injections has assigned responsibility to this molecule, which is obtained from bovine liver. We report an anaphylactic shock probably caused by impurities contained in an orgotein preparation. Prick test to Peroxinorm (orgotein), BSA, and cow liver extract were positive but resulted negative with chymotrypsin, milk, meat and cow epithelium extracts. Tryptase levels determined 3, 24 hours and 15 days after the shock measured 6.32, 0.81 and 0.84 U/L respectively. Detection of specific IgE to Peroxinorm, BSA and chymotrypsin by ELISA was negative and positive to cow liver. Specific IgE to milk and cow epithelium by Pharmacia CAP system was negative. Immunoblotting with Peroxinorm revealed IgE specific bands at an apparent M.W of 67, 51, 56 and 16 kDa; immunoblotting with cow liver revealed bands at 72, 56, 50 and 36 kDa; immunoblotting with BSA and chymotypsin were negative. This case emphasises the role that 20 % of impurities of the pharmaceutical preparation may have in immediate hypersensitivity reactions.
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PMID:Anaphylactic shock caused by impurities in orgotein preparations. 1183 86

PSA complexed with alpha-1-anti-chymotrypsin (cPSA trade mark ) is the moiety in greatest proportion in the serum of men with prostate cancer (CAP). The performance of this analyte has been established primarily in retrospective archival serum. Studies indicate cPSA trade mark provides the specificity enhancement of the free-to-total PSA ratio, yet obviates the need to measure two markers. In the present investigation we sought to establish the stability of cPSA trade mark with long-term storage. Serum from men undergoing ultrasound-guided biopsy was utilized. Serum was assayed soon after collection and 18 months later. All serum was initially aliquotted and stored at -80 degrees C. There was no freeze-thaw. cPSA trade mark was measured utilizing the Bayer Immuno 1 method according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8) and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist between the two determinants (r(2)=1.0, slope=1.01, t-test P=0.9194). These data establish for the first time the long-term stability of cPSA trade mark. Retrospective studies performed on archival material should give meaningful results. Prostate Cancer and Prostatic Diseases (2000) 3, 191-194
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PMID:Long-term stability of alpha-1-antichymotrypsin complexed form of prostate specific antigen. 1249 96