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)

Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases.
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PMID:The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes. 17 70

Homogenates of cultured rat embryo fibroblasts have been assayed for acid phosphatase, N-acetyl-beta-glucosaminidase, cathepsin D, acid deoxyribonuclease, cytochrome oxidase, NADH cytochrome c reductase, 5'-nucleotidase, inosine diphosphatase, acid pyrophosphatase, neutral pyrophosphatase, esterase, catalase, cholesterol, and RNA. The validity of the assay conditions was checked. Neutral pyrophosphatase is a readily soluble enzyme. Acid hydrolases, except acid pyrophosphatase, are particle-bound enzymes, which exhibit a high degree of structural latency. They are activated and solubilized in a parallel fashion by mechanical treatments and tensio-active agents. Catalase is also particle-bound and latent; activating conditions stronger than those for hydrolases are required to activate the enzyme. Acid pyrophosphatase, 5'-nucleotidase and inosine diphosphatase are firmly particle-bound, but not latent; they are not easily solubilized. In differential and isopycnic centrifugation, the latent hydrolases, cytochrome oxidase and catalase dissociate largely from each other; this suggests the occurrence of lysosomes and peroxisome-like structures besides mitochondria. The distribution patterns of 5'-nucleotidase and cholesterol are largely similar; digitonin influences their equilibrium density to the same extent; these two constituents are thought to be related to the plasma membrane. Inosine diphosphatase and acid pyrophosphatase are also partially associated with the plasma membrane, although some part of these enzymic activities probably belongs to other structures. NADH cytochrome c reductase is associated partly with the endoplasmic reticulum, partly with mitochondria.
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PMID:Analytical fractionation of homogenates from cultured rat embryo fibroblasts. 437 90

The paper presents the results of study of 28 synovial exudations in which the uricase method was used for uric acid determination with simultaneous pyrophosphatase and cathepsin C and D activity determination. The presence of crystals in these exudations was investigated as well. From the study follows that a higher uric acid level and higher pyrophosphatase activity coincide with the finding of urate and pyrophosphate crystals. The reported method of examination applies also to other identifications of microcrystals or crystalline split of urates or calcium pyrophosphate dihydrate in the exudation. The activity of cathepsin D permits to conclude on potential participation of peptides and/or polypeptides in the formation of crystals in the exudation.
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PMID:[Study of crystals in synovial exudations with simultaneous determination of adequate enzymes]. 722 82

The enzymatic characterization and analytical fractionation of L1210 cells have been performed in view of studying the cellular pharmacology of antitumoral drugs. Several enzymatic activities were detected and their assay conditions optimized. After a gentle homogenization to preserve as much as possible the integrity of the nucleus and cytoplasmic organelles, homogenates were fractionated by differential and isopycnic centrifugation. On the basis of pH dependency, effect of detergents and distributions after cell fractionation, enzymatic activities and biochemical constituents can be classified in several groups and by analogy to other organs or cultured cells, attributed to distinct cellular components. N-Acetyl-beta-glucosaminidase, alpha-L-fucosidase, alpha-D-mannosidase detected at acid pH and cathepsin D are therefore proposed as markers of lysosomes; inosine diphosphatase and uridine monophosphatase as markers of the plasma membrane, while phosphoglucomutase and neutral pyrophosphatase on one hand and galactosyl transferase and alpha-D-mannosidase at pH 6.0 on the other hand are attributed respectively to the cytosol and the Golgi apparatus.
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PMID:Enzymatic characterization and analytical fractionation of L1210 cells. 723 41

Little is known about the development of the central nervous system (CNS) in humans. Ethical considerations preclude experimental studies in this field, and as a result most available data on human ontogenesis are descriptive. Comparative anatomic and embryologic studies have demonstrated that the main developmental milestones are conserved across species, and their results can be used to suggest a likely scenario for human development. The development of the ventricles, meninges, and choroid plexuses are discussed in this article. The central cavity of the neural tube is formed during neurulation, which occurs during the fourth gestational week. The first milestone is occlusion of the spinal neurocele (the central canal in the neural tube) shortly after neurulation. This prevents free communication between the ventricular system and the amniotic cavity. The second milestone is development of the meninges, which separate the central nervous system from the rest of the body. The embryonic origin of the meninges varies across species. In birds (and probably in mammals), the spinal meninges are derived from the somitic mesoderm, the brainstem meninges from the cephalic mesoderm, and the telencephalic meninges from the neural crest. Differentiation of the meninges, which involves formation of the subarachnoid space, occurs early, before the cerebrospinal fluid (CSF) begins to flow around the CNS. During ontogenesis, the meninges play a key role in regulating the growth of underlying nervous structures. They induce the formation of the superficial glial limiting layer and stimulate the growth of precursors located in the superficial blastemas of the cerebellum and hippocampus. The choroid plexuses are complex specialized structures that produce most of the CSF. Their epithelium derives from the neural tube epithelium and their mesenchyma from the meninges. Of the many enzymes produced in the choroid plexuses, some reflect the pivotal metabolic role of these structures (alkaline and acid phosphatases, magnesium-dependent ATPase, glucose-6-phosphatase, thiamine pyrophosphatase, adenylate cyclase, oxidoreductase, esterases, hydrolases, cathepsin D, and glutathion S-transferase). The two enzymes that are crucial to the production of CSF are Na+/K+ ATPase and carbonic anhydrase. Inactivation of catecholamines is mediated by catechol-O-methyltransferase and by the monoamine oxidases A and B. The morphology and synthesis profile of the choroid plexuses changes during development, although little is known about these changes in humans.
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PMID:Embryonic and fetal development of structures associated with the cerebro-spinal fluid in man and other species. Part I: The ventricular system, meninges and choroid plexuses. 975 71