Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Twelve acid hydrolases, 4 near-neutral hydrolases, and alkaline phosphatase were demonstrated in 0.34 M sucrose homogenates of Trypanosoma cruzi strain Y: p-nitrophenylphosphatase and alpha-naphthylphosphatase, with optimum pH at approximately 6.0; alpha=ga;actpsodase. beta=ga;actpsodase. beta=g;icpsodase, N-acetyl-beta-glucosaminidase, cathepsin A and peptidase I and III, with optimum pH between 5.0 and 6.0; and arylsulfatase, cathepsin D, alpha-arabinase and alpha-mannosidase with optimum pH at approximately 4.0. alpha-Glucosidase, glucose-6-phosphatase and peptidase II had optimum pH at approximately 7.0. beta-Glycerophosphatase had a broad pH-activity curve from 4,0 to 7.4, with maximum activity at pH 7.0. The main kinetic characteristics of these enzymes and their quantitative assay methods were studied. No activity was detected for alpha-fucosidase, beta-xylosidase, beta-glucuronidase, elaidate esterase, acid lipase, and alkaline phosphodiesterase.
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PMID:Acid and neutral hydrolases in Trypanosoma cruzi. Characterization and assay. 4 19

Muscle tissue levels of lysosomal catheptic enzymes, such as cathepsins D, A, B1, C, and dipeptidyl peptidase II, were measured in control subjects and patients with muscular dystrophies, polymyositis, and certain denervating diseases. The results show that, in general, the activities of these enzymes are increased in muscles of patients with muscular dystrophies and other diseases. The increases in cathepsin D and autolytic activities are not significant until the late stage of the disease process. Cathepsins A, B1, and C are, however, significantly elevated in mildly affected dystrophic and other diseased muscles. Of these catheptic enzymes, cathepsin B1 displays the highest rise at an early stage, suggesting that it may be one of the rate-controlling enzymes of proteolysis. Dipeptidyl peptidase II is increased slightly in dystrophic and other myopathic muscles but is unchanged in denervated muscle. These data clearly implicate the lysosomal group of proteinases as largely responsible for mediating muscle breakdown in the muscular dystrophies and certain other muscle and neuromuscular diseases in man.
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PMID:Muscle breakdown and lysosomal activation (biochemistry). 28 25

The purity of cathepsin D has been increased from 150 units/mg to over 200 units/mg. Peptides such as Ala-Phe-NH2, His-Phe-NH2 and Phe-Phe were split by impure enzyme and activity was blocked by pepstatin and diazoacetylnorleucine methyl ester. Pure preparations no longer digested these peptides. This points to the presence of a second peptidase activity similar to cathepsin D in specificity and inhibition properties, but distinct from it . Cathepsin D splits the peptides Leu-Phe-NH2, Leu-Tyr-NH2, Ac-Phe-TyrI2, and Ala-Leu-Tyr-Leu upon overnight incubation. More rapid splitting is found with phenyl sulfite, Glu-Ala-Leu-Tyr-Leu-Val, and Bz-Arg-Gly-Phe-Phe-Leu-4-methoxy-beta-naphthylamide. Digestion of bovine hemoglobin and human serum albumin by ruptured rat liver tritosomes was studied over the pH range 2.5-6.5. The combined action of cathepsin D and thiol proteinases accounted for most of the digestion. Cathepsin D accounted for 75% of the hemoglobin digestion at pH 3 and 45% at pH 5. Thiol proteinase accounted for 85% of the albumin digestion at pH 5. The role of cathepsin D in the development of embryonic limbs and skin, in uterine involution, and in cartilage degradation was reviewed. The activity of cathepsin D on cartilage matrix proteoglycans is limited to acid pH values. Human articular cartilage also contains metalloproteases active at pH 4.5 and 5.7.
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PMID:Specificity and biological role of cathepsin D. 59 4

The NH2-terminal heterogeneity which is generated in bovine GH during its extraction from mildly acidified pituitary homogenates is attributable to a newly identified peptidase. The beta-naphthylamide of Phe-Pro-Ala, modeled after the NH2-terminal tripeptide sequence of the phenylalanyl monomer of bovine growth hormone, was cleaved by the peptidase into the tripeptide and B-naphthylamine and served as a substrate for assay of the eznyme. However, the B-naphthylamide of Ala-Phe-Pro, modeled after the NH2-terminal tripeptide sequence of the alanyl monomer, was not cleaved. In harmony with this specificity, the peptidase cleaved 11 tripeptides sequentially from the NH2-terminus of the phenylalanyl monomer of bovine GH but none from the alanyl monomer. Six of the tripeptides nearest the NH2-terminus were unequivocally identified and their sequences were consistent with the NH2-terminal octadecapeptide sequence of the phenylalanyl monomer of bovine GH. Five additional peptides were by composition consistent with their being tripeptides derived from residues 19--33. Because of the apparent specificity for the hydrolytic release of tripeptides and inability to cleave substituted tripeptidyl derivatives, the enzyme is considered to be a tripeptidyl aminopeptidase. In its hydrolysis of phenylalanyl monomers of rat growth hormone, a similar number of tripeptides was released, associated with which there was a 70% loss of biological activity but no reduction in immunological activity. The enzyme could be solubilized by extraction with 1% Triton X-100 at pH 3.0, precipitated between 2 and 3 M (NH4)2SO4, and further purified by gel filtration on G-75 in M/10 acetic acid. The enzyme has a mol wt of 57,000 and is optimally active at pH 4. It can be differentiated from cathepsin D by its insensitivity to inhibition by pepstatin.
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PMID:Identification of a tripeptidyl aminopeptidase in the anterior pituitary gland: effect on the chemical and biological properties of rat and bovine growth hormones. 74 18

1. Intact parenchymal and non-parenchymal cells were isolated from rat liver. The parenchymal cells were purified by differential centrifugation, while non-parenchymal cells were obtained free of parenchymal cell contamination by preferentially destroying the parenchymal cells with the aid of pronase (0.25%). 2. The ability to isolate pure intact parenchymal and non-parenchymal cells permitted the characterization and measurement of specific activities of various lysosomal enzymes, representing the main functional hydrolytic activities of the lysosomes in these distinct cell types. 3. Lysosomal enzymes catalysing the hydrolysis of the terminal carbohydrate moiety of glycoproteins and glycolipids were not particularly enriched in the non-parenchymal cells as compared to parenchymal cells. The ratio of the specific activities of non-parenchymal cells over parenchymal cells varied between 0.7 for N-acetyl-beta-D-hexoseaminidase to 2.1 for alpha-glucosidase. This suggests no specific role of the non-parenchymal cells in the hydrolysis of terminal carbohydrate moieties of glycoproteins and glycolipids. 4. The enzymes acid phosphatase and aryl sulphatase, representing the phosphate and sulphate hydrolyzing activities, were enriched in the non-paranchymal cells as compared to the parenchymal cells by a factor of 2.5. 5. The most important peptidase cathepsin D, representing protein breakdown capacity, is enriched in the non-parenchymal cells as compared to parenchymal cells by a factor 6.0, suggesting a possible specific function of non-parenchymal cells in protein breakdown. 6. The most enriched lysosomal enzyme, representing lipid hydrolysis, is acid lipase, which is enriched in the non-parenchymal cells with a factor of 10. 7. The distribution of lysosomal enzymes between parenchymal and non-parenchymal cells suggests different functional roles of the lysosomes in these cell types. It can be concluded that the non-parenchymal cells possess a set of lysosomal enzymes which makes them extremely suitable for a phagocytic and antimicrobial function in the liver.
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PMID:Identity and activities of lysosomal enzymes in parenchymal and non-parenchymal cells from rat liver. 118 30

Unicameral bone cyst fluid possesses N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, PZ-peptidase, cathepsin D, acid phosphatase, N-acetyl-beta-D galactosaminidase, and beta-galactosidase activities. The activities of lysosomal enzymes in the cyst fluid are, as a rule, higher than in the serum, whereas the total protein content is lower. The content of collagen degradation products in the cyst fluid is higher compared to the serum. In bone cavity wall tissues, the collagen content is decreased. Adenosine 3':5'-cyclic phosphate and cyclic guanosine 3,5'-monophosphate accumulate in the cyst cavity. However, in some cases, there is no correlation among the activities of lysosomal enzymes in the cyst fluid, blood serum, and cyst wall tissues. The ratios of lysosomal enzyme activities in the cyst fluid differ from those in the cyst wall tissues, cultured skin fibroblasts, and blood polymorphonuclear leucocytes. The lack of coincidence of enzymatic spectra of the cyst fluid, wall tissues, and serum is suggestive of the diversity of ways of lysosomal enzyme enter the cyst cavity, i.e., blood, cyst fluid cells, and cyst cavity walls. The cysts with different locations (i.e., active and latent cysts) have similar lysosomal lytic potentials. The presence in the cyst cavity of extracellular lysosomal enzymes and collagen degradation products testifies to the permanent corrosion of the cyst cavity walls from the inside as well as to the increase in the osmotic pressure of the cyst fluid. Lysosome destruction should be regarded as an important pathogenetic factor that requires surgical or pharmacologic correction or both in the course of bone cyst management.
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PMID:The role of lysosomes in the pathogenesis of unicameral bone cysts. 185 Mar 36

It was the purpose of this study to define the chromogranin A-processing proteinases present in highly purified preparations of bovine chromaffin granules. The most active enzyme had a pH optimum of 5.0 and was inhibited by pepstatin. It could be identified immunologically as a cathepsin D-like enzyme and subcellular fractionation established its lysosomal origin. After removal of this enzyme the remaining activity at pH 5.0 was mainly due to a cathepsin B-like proteinase. The presence of this enzyme could also be attributed to lysosomal contamination. In the presence of calcium, a further proteolytic activity became apparent at pH 5.0. This enzyme which was inhibited by rho-chloromercuriphenylsulfonic acid was localized in chromaffin granules. A trypsin-like peptidase, most active at pH 8.2, was enriched in a membrane wash of chromaffin granules. Subcellular fractionation indicated that this enzyme is preferentially bound to the membranes of very dense particles probably representing a subpopulation of chromaffin granules. This study establishes that the most active chromogranin A-degrading proteinases present in highly purified chromaffin granules are attributable to lysosomal contamination. Two enzymes with low activity (a Ca2+ activated proteinase and a trypsin-like enzyme) are, apparently, true constituents of chromaffin granules.
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PMID:Chromogranin A-processing proteinases in purified chromaffin granules: contaminants or endogenous enzymes? 215 64

When the distribution profile of hydrolases in mycelial homogenates and culture filtrates of A. parasiticus and A. flavus was examined, six hydrolytic enzymes viz. N-acetyl-beta-glucosaminidase, aryl sulfatase, alkaline proteinase, cathepsin B, cathepsin D and aminopeptidase were detected in homogenate. The culture filtrates were devoid of any activity of these enzymes. The enzyme levels varied with the stage of incubation. The most abundant fungal exopeptidase showing preference for basic amino acid naphthylamides seems to be an aminopeptidase B. Incorporation of CEPA, an ethylene generating compound, stimulated the amino peptidase activity in the mycelium but inhibited the enzyme in vitro. The enzyme was also inhibited by different aflatoxins to varying degree. While aminopeptidase B was located intracellularly, a non-dialysable, heat-stable inhibitor of the enzyme was found to be secreted in the culture filtrate. This peptide inhibitor was however ineffective on the other enzymes.
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PMID:Intracellular hydrolases of Aspergillus parasiticus and Aspergillus flavus. 249 93

The suitability of Z-Arg-Gly-Phe-Phe-Leu-MNA and Z-Arg-Gly-Phe-Phe-Pro-MNA for the assessment of cathepsin D activity was tested in biochemical and histochemical experiments. Substrates were dissolved in dimethylformamide and used at 0.1-0.5 mM in various buffers over a pH range of 3.5-7.4. Homogenates of various rat organs and isolated purified enzymes [cathepsin D from bovine spleen, dipeptidyl peptidase (DPP) IV from porcine kidney and rat lung] were used as enzyme sources. Pepstatin, di-isopropylfluorophosphate (DFP), p-chloromercuribenzoate, o-phenanthroline and a series of DPP IV inhibitors were used in inhibitor experiments. At pH 3.5 and 5.0, substrates were used in a two-step postcoupling procedure with aminopeptidase M and dipeptidyl peptidase IV as auxiliary enzymes and Fast Blue BB as coupling agent. Results were compared with those obtained with haemoglobin. Above pH 5.0 substrates were used in a one-step postcoupling procedure. Cryostat sections of snap-frozen or cold aldehyde-fixed tissue pieces of various rat organs and biopsies of human jejunal mucosa were used in histochemical experiments. As in biochemical tests a two-step procedure was used in the pH range 3.5-5.0, but Fast Blue B was used in the second step for the simultaneous coupling. Above pH 5.0 a one-step simultaneous azo coupling procedure was used with Fast Blue B as coupling agent. At pH 3.5 the hydrolysis rate of both synthetic substrates was about 100x lower than that of haemoglobin when cathepsin D from bovine spleen was used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Are Z-Arg-Gly-Phe-Phe-Leu-MNA and Z-Arg-Gly-Phe-Phe-Pro-MNA suitable substrates for the demonstration of cathepsin D activity? 289 46

The specificity of action of bovine brain cortex cathepsin D (EC 3.4.23.5) and high-Mr aspartic endopeptidase (EC 3.4.23.-) was studied with the vasoactive peptides renin substrate tetradecapeptide (RSTP), substance P (SP), and angiotensins I and II, and with model peptides--Lys-Pro-Ala-Glu-Phe-Phe (NO2)-Ala-Leu (I), Gly-Gly-His-Phe (NO2)-Phe-Ala-Leu-NH2 (II), and Abz-Ala-Ala-Phe-Phe-pNA (III). Cerebral aspartic peptidases show identical substrate specificity, cleaving the Leu10-Leu bond in RSTP and Phe-Phe in SP and peptide I-III, and not splitting angiotensins I and II. Because of the higher catalytic efficiency of cathepsin D (Kcat value), the specificity constants (Kcat/Km) for cathepsin D-catalyzed hydrolysis of substrates 1-111 are much higher than those for the high-Mr enzyme. High-Mr aspartic peptidase shares a number of properties with cathepsin D (sensitivity to pepstatin, substrate specificity, pH activity profile) and shows partial immunological identity; however, high-Mr aspartic peptidase has a specific activity 7-10 times lower than that of cathepsin D. The kinetic parameters of proteolysis of model peptides presented indicate that the high-Mr enzyme may be a complex of a single-chain cathepsin D with another polypeptide, although the possibility that it is an independent aspartic peptidase cannot be excluded.
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PMID:Substrate specificity of cerebral cathepsin D and high-Mr aspartic endopeptidase. 328 13


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