Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specific enzymic properties, membrane or particle binding capacities, and the total activities of certain acid hydrolases, including cathepsin D, acid phosphatase, arylsulfatase, and five acid glycosidases have been compared in normal canine antral and fundic mucosae and in liver. The two major regions of the gastric mucosa, whose cell populations are comparable in type but have very distinct functions, also differ in many properties of their lysosomal enzymes. These differences necessitate several major modification in their method of assay. Using optimal conditions, the activities of most of these enzymes were found to differ: levels in the antrum, in spite of its high water and mucin-glycoprotein content, were significantly greater, suggesting that the high lysosomal hydrolytic activity may be associated with the rapid autophagic processes of normal turnover of its surface epithelial and mucous neck cells. Lysosomal membrane stability or latency is also greater in the antrum; this may account, in part at least, for antral resistance to erosions brought about by stress.
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PMID:Acid hydrolases. Assay of activity and latency in the varied mixed cell populations of canine gastric mucosa. 1 64

Patients with the DMC syndrome have been suggested to possess a specific sulfatase abnormality and/or to be deficient in a proteinase cleaving glycoprotein-acid mucopolysaccharide (AMP) linkage. We have previously found in DMC patients an abnormal excretion of urinary AMPs of which hyaluronic acid and chondroitin sulfate (A + C) were oversulfated and keratosulfate and heparan sulfate were undersulfated. Lysosomal acid proteinase, i.e. cathepsin D (EC 3.4.23.5) and neutral proteinase : elastase (EC 3.4.21.11) and cathepsin G were found to be normal in DMC patients. However, alpha 2-macroglobulin in serum was raised. This increase may be associated with a complex formation of alpha 2-macroglobulin with a neutral proteinase released from the cells. Increased levels of chondroitin sulfate N-acetylgalactosamine-6-sulfate sulfatase and sulfamidase and decreased enzymic levels of arylsulfatase A and B (EC 3.1.6.1) were found in leucocytes of DMC patients. The sulfatase activities assayed in the present study support our theory that a specific sulfatase abnormality may exist in the DMC syndrome.
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PMID:Lysosomal (leucocyte) proteinase and sulfatase levels in Dyggve-Melchior-Clausen (DMC) syndrome. 7 86

Cathepsin D was originally known simply as 'cathepsin' and was first purified in the late 1930s. Nowadays the enzyme is purified by conventional column chromatography, and by isoelectric focusing (which resolves isoforms), but affinity chromatography with pepstatin--Sepharose is also important. Cathepsin D is a glycoprotein of about 42,000 molecular weight; sometimes it comprises a single polypeptide chain but often this is found to have been 'nicked' about two-thirds of the way from one end. Cathepsin D is an 'aspartic proteinase' and may be one of the more primitive members of the family. The activity of cathepsin D is expressed exclusively at acidic pH values and the specificity shows a strong preference for cleavage near hydrophobic amino acids. Specific inhibition of cathepsin D with antibodies and pepstatin has provided strong evidence that the enzyme plays a part in intralysosomal proteolysis but there is as yet little evidence for extracellular activity.
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PMID:Cathepsin D: the lysosomal aspartic proteinase. 39 96

The Dyggve-Melchior-Clausen (DMC) syndrome includes short stature, dwarfism, mental retardation, and skeletal abnormalities especially in the spine and the extremities resembling the findings in the mucopolysaccharidoses. A particular abnormality is the "lace border" found on radiological examination of the iliac crest. The three original cases have been followed for 15--20 years and the course is characterized by increasing mental retardation and motor disability whereas the "lace border" is less pronounced than before. A survey of 17 other cases is given and similarities and differencies to the mucopolysaccharidoses are pointed out. Patients with the DMC syndrome have been suggested to be deficient in an enzyme cleaving glycoprotein-acid mucopolysaccharide (AMP) linkage. We have previously found in DMC patients, an abnormal excretion of urinary AMP's of which some were undersulfated and some were oversulfated. Lysosomal acid proteinase, i.e., cathepsin D and neutral proteinases: elastase and cathepsin G were found to be normal in DMC patients. However, alfa2-macroglobulin in serum was raised. This increase may cause an inhibition of the neutral proteinases. An increased level of chondroitin sulfate N-acetylgalactosamine-6-sulfate-sulfatase and decreased enzymic levels of aryl sulphatase A and B (assayed with p-nitrocatecholsulfate as a substrate) were found in leucocytes of DMC patients. Metabolic studies have revealed an unbalanced incorporation of glycoprotein AMP-precursors in DMC lymphocytes. All in all the data suggests the DMC syndrome to be an inborn error of glycoprotein-AMP-metabolism.
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PMID:The Dyggve-Melchior-Clausen (DMC) syndrome. A 15 year follow-up and a survey of the present clinical and chemical findings. 57 40

Cathepsin D was purified from human liver by a procedure involving autolysis, acetone fractionation, and chromatography on ion-exchange media and organomercurial-sepharose. Multiple forms of the enzyme were then separated by preparative isoelectric focusing. The molecular weight of the protein was found to be 43,000. Its amino acid composition was determined and it was shown to be a glycoprotein. When treated with sodium dodecyl sulphate or chaotropic agents (without reduction) all forms of the enzyme tested gave components of about 28,000 and 14,000 molecular weight. Specific antisera were raised against the enzyme, and the characteristics of immunoinhibition were investigated. Immuno-inhibition of rabbit cathepsin D within living macrophages was shown to interfere with degradation of some proteins endocytosed by the cells. The antisera against human and rabbit cathepsin D were used in immunofluorescent localization of the enzyme in sites of tissue damage in which cathepsin D might be implicated. The characteristics of inhibition of human cathepsin D by pepstatin were established. At pH values below 5, KD values of 5 x 10(-10)M were determined and pepstatin was shown to be an excellent titrant for cathepsin D. In the range pH 5-6.4 DK increased steeply and it was concluded that the binding site for substrate and inhibitor was abolished by a conformational change in the enzyme molecule in which three protons are lost.
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PMID:Human cathepsin D. 59 2

Horse spleen cathepsin D (3.4.23.5.) was purified from crude extract by sodium chloride and ethanol precipitation, column chromatography fractionation on DEAE cellulose and CM Sephadex, re-chromatography on DEAE cellulose and gel filtration. The enzyme has been purified about 3.000 folds with a yield of 30 per cent. The purified enzyme seems to be homogeneous on Sephadex G100, one protein band is apparent on disc electrophoresis. Determined by dansylation the N-terminal amino acid is glycine. A molecular weight of 42,500 +/- 3,000 was obtained with Sephadex G100 gel filtration and light scattering measurements. Amino acid analysis and chemical determinations were performed: cathepsin D is a glycoprotein (2 or 3 osamine residues) including 344 amino acids and 4 disulfide bonds. Spectrophotometric data show that E1cm/1 mg/ml = 1.01 at lambda = 280 nm. ORD measurements indicate about 20 per cent of helicoidal content in the molecule.
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PMID:[Cathepsin D from horse spleen. I. Purification and study of certain physicochemical properties]. 97 59

The kinetic properties of UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) partially purified from the soil amoeba Acanthamoeba castellanii have been studied. The transferase phosphorylated the lysosomal enzymes uteroferrin and cathepsin D 3-90-fold better than nonlysosomal glycoproteins and 16-83-fold better than a Man9GlcNAc oligosaccharide. Deglycosylated uteroferrin was a potent competitive inhibitor of the phosphorylation of intact uteroferrin (Ki of 48 microM) but did not inhibit the phosphorylation of RNase B or the simple sugar alpha-methylmannoside. Deglycosylated RNase (RNase A) did not inhibit the phosphorylation of RNase B or uteroferrin. These results indicate that purified amoeba GlcNAc-phosphotransferase recognizes a protein domain present on lysosomal enzymes but absent in most nonlysosomal glycoproteins. The transferase also exhibited a marked preference for oligosaccharides containing mannose alpha 1,2-mannose sequences, but this cannot account for the high affinity binding to lysosomal enzymes. A. castellanii extracts do not contain detectable levels of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, the second enzyme in the biosynthetic pathway for the mannose 6-phosphate recognition marker. We conclude that A. castellanii does not utilize the phosphomannosyl sorting pathway despite expression of very high levels of GlcNAc-phosphotransferase.
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PMID:Characterization of UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase from Acanthamoeba castellanii. 131 74

We have developed an efficient method for labeling the Asn-linked oligosaccharides of recombinant glycoproteins synthesized in Xenopus laevis oocytes. By coinjecting GDP-[3,4-(3)H]mannose with mRNA for human cathepsin D, it was possible to incorporate as much as 1800 cpm per oocyte into each of the two Asn-linked oligosaccharides of this glycoprotein. Overall, about 50% of the microinjected GDP-[3,4-(3)H]mannose was incorporated into Asn-linked oligosaccharides, a 10-fold greater value than that obtained when [2-(3)H]mannose was microinjected. Less than 10% of the injected GDP-[3,4-(3)H]mannose was metabolized to water or converted to amino acids. This technique should facilitate studies of Asn-linked oligosaccharide biosynthesis, processing, and structure in recombinant proteins synthesized in Xenopus oocytes.
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PMID:A method for [3H]mannose labeling of Asn-linked oligosaccharides on recombinant glycoproteins synthesized in Xenopus oocytes. 144 67

Endocytosis of tissue-type plasminogen activator (t-PA) by different types of rat liver cells was studied in immunocytochemically labelled cryosections as well as in biochemical experiments. For morphological localization of the ligand in different endocytic compartments involved in its catabolism, rat livers were fixed at various times (1-24 min) after injection of t-PA. Late-endosomal and lysosomal compartments were identified by double-labelling the sections with antibodies to the lysosomal proteins glycoprotein Igp 120 and cathepsin D. In liver t-PA was localized in sinusoidal endothelial cells (EC), parenchymal cells (PC) and to some extent in Kupffer cells (KC), indicating that it is internalized and degraded in all three cell types. In specimens fixed 6 min after injection PC, EC and KC were found to contribute to 69, 24 and 7% respectively of total t-PA endocytosed. The transfer from late endosomes to lysosomes was found to be faster in EC than in PC. The morphological findings were supported by studies of the endocytic mechanisms employing isolated perfused livers and primary hepatocytes. The presence of monensin, an inhibitor of lysosomal protein degradation, reduced the amount of t-PA degraded to about 50% of the control values. The catalytic site seems not to be required for the catabolism of t-PA in hepatic cells. The inhibition of t-PA by D-phenylalanyl-L-prolylarginyl-chloromethane did not influence receptor recognition and catabolic processing, as determined in morphological studies using labelled cryosections, in binding studies employing liver cell membranes and primary hepatocytes, as well as in liver-perfusion experiments.
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PMID:Endocytosis and intracellular processing of tissue-type plasminogen activator by rat liver cells in vivo. 155 69

The localization of MHC class II molecules (Ia) was studied by ultrastructural immunocytochemistry in murine bone marrow-derived macrophages stimulated by recombinant interferon-gamma (rIFN-gamma). Ia molecules were detected on the plasma membrane and on the limiting membrane and internal structures of vesicular acidic compartments. Some of these vesicules also contained cathepsin B and/or cathepsin D. The use of BSA-gold, a marker of fluid phase endocytosis, allowed the identification of Ia-positive organelles as endocytic compartments. The first to be labelled with BSA-gold also contained the cation-independent mannose 6-phosphate receptor (MPR) but not the 120,000 molecular weights lysosomal glycoprotein (lgp 120). Later on, BSA-gold appeared in Ia+, MPR+, lgp 120+ compartments. Collectively these data suggest that intracellular Ia molecules are mainly present in early and late endosomes.
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PMID:Localization of MHC class II molecules in murine bone marrow-derived macrophages. 184 71


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