Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A ('angiotensin-converting enzyme') and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.
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PMID:Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid. 265 79

Renal dipeptidase (EC 3.4.13.11) was solubilized from pig kidney microvillar membranes with bacterial phosphatidylinositol-specific phospholipase C and then purified by affinity chromatography on cilastatin-Sepharose. The enzyme was apparently homogeneous on SDS/polyacrylamide-gel electrophoresis with an Mr of 47,000. Immunohistochemical analysis of the distribution of the dipeptidase showed it to be concentrated in the brush-border region of the proximal tubules in close association with endopeptidase-24.11) (EC 3.4.24.11). The purified dipeptidase was shown to contain 1 mol of inositol/mol and to possess the cross-reacting determinant characteristic of the glycosyl-phosphatidylinositol membrane-anchoring domain. The glycoprotein nature of renal dipeptidase was confirmed by chemical and enzymic deglycosylation. These results establish renal dipeptidase as a glycosyl-phosphatidylinositol-anchored ectoenzyme of the microvillar membrane.
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PMID:Ectoenzymes of the kidney microvillar membrane. Affinity purification, characterization and localization of the phospholipase C-solubilized form of renal dipeptidase. 293 Apr 55

Renal localization of radiolabeled antibody fragments presents a problem in targeted imaging and radiotherapy. We recently reported that Fab fragments labeled with 3'-[(131)I]iodohippuryl N(epsilon)-maleoyl-l-lysine (HML) demonstrated markedly low renal radioactivity levels from early postinjection in mice. Previous studies suggested that low renal radioactivity levels were attributable to cleavage of the glycyl-lysine sequence in HML by the action of renal brush border enzymes, followed by urinary excretion of the resulting m-iodohippuric acid. In this study, an in vitro system using brush border membrane vesicles (BBMVs) isolated from the rat kidney cortex was developed to estimate renal brush border enzyme(s)-mediated cleavage of the peptide linkage. Low molecular weight HML derivatives, 3'-[(125)I]iodohippuryl l-lysine (HL), 3'-[(125)I]iodohippuryl N(epsilon)-tert-butoxycarbonyl-l-lysine (HBL), and their d-amino acid counterparts, were synthesized and incubated in BBMVs. Both [(125)I]HL and [(125)I]HBL generated m-[(125)I]iodohippuric acid after incubation in BBMVs at 37 degrees C while the latter liberated significantly higher amounts of the metabolite. [(125)I]d-HL and [(125)I]d-HBL failed to release the metabolite under similar conditions. The liberation of m-[(125)I]iodohippric acid from [(125)I]HL was significantly facilitated or completely inhibited by the addition of an activator or an inhibitor for carboxypeptidase M. The release of m-[(125)I]iodohippuric acid from [(125)I]HBL increased by the addition of the activator, whereas the inhibitor partially inhibited the release of the metabolite from [(125)I]HBL. The BBMV-mediated release of m-[(125)I]iodohippuric acid from [(125)I]HBL was not impaired by the addition of inhibitors for neutral endopeptidase or renal dipeptidase. These findings showed that the glycyl-l-lysine sequence in HML would be recognized and cleaved by metalloenzymes and nonmetalloenzymes on the renal brush border even when iodine was incorporated into a benzene ring and the N(epsilon)-amine residue of lysine was chemically modified, which supported the hypothesis that low renal radioactivity levels of HML-conjugated Fab fragments would be attributed to the release of m-iodohippuric acid by renal brush border enzymes. This study suggested that this in vitro system using BBMVs would be useful to estimate radiolabeling reagents of antibody fragments or peptides designed to reduce renal radioactivity with a variety of radionuclides.
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PMID:In vitro system to estimate renal brush border enzyme-mediated cleavage of Peptide linkages for designing radiolabeled antibody fragments of low renal radioactivity levels. 1628 61