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

The activities of a number of peptide-degrading enzymes were compared in homogenates of GH3 cells and rat anterior pituitaries. The enzymes studied were prolyl endopeptidase (EC 3.4.21.26), a soluble metalloendopeptidase, pyroglutamyl peptide hydrolase (EC 3.4.11.8), a multicatalytic protease complex, cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5), aminopeptidase (EC 3.4.11.2), and a membrane-bound neutral metalloendopeptidase (EC 3.4.24.11). Specific substrates were used to measure the activities, and active-site-directed inhibitors were used to verify the identities of the enzymes studied. Of the two lysosomal enzymes studied, cathepsin B, the enzyme with the highest activity in both preparations, had 5 times the activity in GH3 cell homogenates as in anterior pituitary homogenates. Cathespin D had a somewhat higher activity in the anterior pituitary homogenates than in the GH3 cell homogenates. Soluble metalloendopeptidase and prolyl endopeptidase, both cytoplasmic enzymes, had about twice the activity in GH3 cell homogenates as in anterior pituitary homogenates. Membrane-bound neutral metalloendopeptidase in the GH3 cell homogenates had 25% of the activity of the anterior pituitary homogenates. Of the two TRH-degrading enzymes, the activity of prolyl endopeptidase in GH3 cell homogenates was about 25 times higher than that of pyroglutamyl peptide hydrolase. Since the secretory function of the pituitary is in part controlled by neuropeptides, the knowledge of the enzyme profiles of the GH3 cells and the anterior pituitary should be of value in studying the metabolism of neuropeptides and peptide hormones in these systems.
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PMID:Peptide-degrading enzymatic activities in GH3 cells and rat anterior pituitary homogenates. 636 4

Secretory vesicles purified from the neural and intermediate lobes of the bovine pituitary contain acidic endopeptidases which are capable of converting renin tetradecapeptide (RTD) substrate to Angiotensin I (AI). Preliminary characterization of the neurosecretory vesicle (NSV) endopeptidase showed that it had a pH optimum of 4.0, and unlike renin was inactive at pHs greater than 6.0. It is inhibited by 10(-6) M pepstatin A, but not by PMSF, leupeptin, PMBS, or the specific renin inhibitor H-142. This NSV endopeptidase differed from cathepsin D in that it was unable to degrade alpha-casein, but was quite active in generating AI from RTD (Vmax = 5 moles/g protein/hour). No enzyme activity that could convert AI to Angiotensin II could be detected in the NSVs suggesting that the acidic endopeptidase is involved in processing neurosecretory vesicle proteins other than those associated with the renin angiotensin system in the brain.
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PMID:Angiotensin I-generating acid endopeptidase activity in neurosecretory vesicles isolated from bovine pituitary. 639 22

The unknown enzymatic mechanism of enhanced protein breakdown in steroid myopathy was studied in functionally and biochemically different muscles of rabbits treated with dexamethasone for three weeks. After glucocorticoid administration the fast-twitch glycolytic semimembraneous muscle of treated animals was atrophied, whereas the weight of the slow-twitch oxidative soleus muscle was not altered. The specific activity of the lysosomal endo- and exopeptidases (cathepsin D, E, B and L, lysosomal carboxypeptidase A and dipeptidylpeptidase I) was increased about 2-fold in the atrophied white muscle. The activity of the cytosol enzyme Ca++-activated neutral proteinase was also elevated, whereas that of the other cytosol endopeptidase, chymotrypsin-like enzyme, was unaltered. The level of alanine aminopeptidase was only slightly increased. On the other hand, there were no unequivocal changes in protease activity in the soleus muscle. These findings are in agreement with the known differences in glucocorticoid-sensitivity of the various muscles. Our results suggest that the lysosomal proteolytic system and the Ca++-activated neutral proteinase may play an important role in the glucocorticoid-induced intracellular protein catabolism in muscle. The inhibitor capacities of cathepsin B and trypsin detectable in muscle cytosol were not altered after steroid treatment. Consequently, the increase in cathepsin B activity was not due to the loss of its inhibitor.
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PMID:Proteases and proteinase inhibitors in experimental glucocorticosteroid myopathy. 676 81

The present study was performed to investigate the enzymatic changes in dystrophic chickens compared to those of dystrophic mice. The activities of 14 kinds of aminopeptidases, 5 kinds of endopeptidase, 4 kinds of glycosidases, phosphatase, esterase, and ribonuclease were measured in muscles of control and dystrophic chickens. When the enzyme activities were expressed as specific activity per unit weight of organs, only some of them were found to be significantly elevated in dystrophic chickens; e.g., alanine aminopeptidase (Ala-AP), Gly-AP and cathepsin D. On the contrary, the activities of alpha-D-glycosidase, alpha-D-galactosidase and alpha-D-mannosidase were significantly decreased. Muscular protein contents of dystrophic chickens also tended to be lower than those of controls. These observations offer a striking contrast with the one obtained in the study on dystrophic mice. However, when expressed as specific activity per mg protein, many enzyme activities were found to be significantly elevated suggesting an extensive abnormality of metabolism in dystrophic chickens. Among 14 kinds of aminopeptidase activities, highly significant elevations were seen especially in AP-A, AP-B, Gly-AP, Ala-AP, Ser-AP, Pro-AP, Leu-AP, Met-AP and Trp-AP. Interestingly enough, a statistical approach suggested a significant correlation between the aminopeptidase changes of dystrophic chickens with those of dystrophic mice. In addition to aminopeptidases, there were highly significant increases in the activities of cathepsin D, alpha-D-glucosidase, beta-D-galactosidase, alpha-D-mannosidase, esterase and RNase. These results indicate that the intramuscular metabolic abnormality of dystrophic chickens are generally different from but partly resembled with those of dystrophic mice.
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PMID:Intramuscular enzyme abnormalities of dystrophic chickens compared to those of dystrophic mice. 701 13

Previous studies have demonstrated that trypan blue directly inhibits thyroid secretion when the dye is administered in vitro or in vivo. To further study the mechanisms of inhibition, cathepsin D (EC 3.4.23.5) (thyroidal acid proteinase) has been purified from bovine thyroid. Trypan blue inhibited the proteolysis of both 125I-labeled thyroglobulin and 125I-labeled hemoglobin in both crude lysosomal enzyme preparation and purified endopeptidase and the inhibition was competitive. Inhibition was also observed when the dye was allowed to prebind to either purified enzyme or purified substrate. Inhibition of cathepsin D is shown to account for part of the inhibition of thyroid secretion.
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PMID:Effects of trypan blue on thyroid secretion. Inhibition of purified cathepsin D from bovine thyroid. 702 45

The dipsogenic activity of two artificial renin substrates, tetradecapeptide and tridecapeptide, was studied. The dose-response curves obtained with these peptides, following intracerebroventricular administration, were similar to that of angiotensin I. The angiotensin II antagonist, Sar1, Ala8-angiotensin II, inhibited the dipsogenic effect of tetradecapeptide, indicating the conversion of the latter peptide into angiotensin II. The lower dipsogenic activity of tridecapeptide points to a conversion of this renin substrate into angiotensin III. Specific inhibition of tetradecapeptide induced drinking by the endopeptidase inhibitor N-acetyl-pepstatin suggests the involvement of an endopeptidase in the conversion of the renin substrates in the brain. Two endopeptidases present in the brain (cathepsin D and renin), were compared with respect to their capacity to generate angiotensin I from artificial renin substrate in vitro. Cathepsin D was active under only acidic pH conditions, whereas renin showed a wider pH range with maximal activity in the non-acidic region. Moreover, cathepsin D did not generate angiotensin I from natural, cerebrospinal fluid-angiotensinogen in vitro, and lacked dipsogenic activity following central administration. Small amounts of renin, however, were able to release angiotensin I from cerebrospinal fluid in vitro. In addition, this enzyme induced high dipsogenic activity upon intracerebroventricular injection. These results support the existence of a functionally active central renin-angiotensin system and provide an argument against the involvement of cathepsin D in the formation of angiotensin I in the brain.
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PMID:Angiotensin generation in the brain and drinking: indications for the involvement of endopeptidase activity distinct from cathepsin D. 702 65

The generation of angiotensin I from the artificial renin substrate tetradecapeptide by proteolytic enzymes in rat brain tissue was studied. The involvement of endopeptidase activity in the enzymatical cleavage of the renin substrate was inferred from the simultaneous accumulation of both angiotensin I and the complementary tetrapeptide Leu-Val-Tyr-Ser on incubation of tetradecapeptide with rat brain tissue. This endopeptidase activity was active over a pH range of 3.5--7.5. In contrast, cathepsin D released angiotensin I from tetradecapeptide only at acidic pH. The angiotensin I accumulation on incubation of tetradecapeptide with brain endopeptidase activity was only partly inhibited in the presence of an excess of the carboxyl protease inhibitor N-acetyl pepstatin. Further, the brain endopeptidase activity displayed a subcellular localization different from that of acid protease activity. It is concluded that angiotensin I can be generated in the brain by soluble endopeptidases, which are distinct from cathepsin D.
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PMID:Subcellular localization in rat brain of angiotensin I-generating endopeptidase activity distinct from cathepsin D. 703 49

We have obtained evidence of thiol endopeptidases in the thyroid which are active in thyroglobulin degradation in vitro. Four pepstatin-insensitive endopeptidase fractions were distinguished in extracts of rabbit thyroids by gel filtration on Bio-Gel A-0.5m. An enzyme from one fraction was obtained in highly purified form and was found to be identical to cathepsin B described in other tissues. Endopeptidases in the three remaining fractions were designated as cathepsins 180K, 110K, and 45K, respectively, on the basis of their estimated molecular size. These were partially purified by either organomercurial affinity chromatography or DEAE-cellulose chromatography. They are identified as thiol endopeptidases on the basis of their sensitivity to inhibition by both leupeptin and the thiol-blocking agent iodoacetic acid and by their activation with the reducing agent glutathione. Each is distinguished from cathepsin B on the basis of molecular size and limited ability to hydrolyze benzoylarginine-2-naphthylamide. The action of the thiol endopeptidases on [125I]thyroglobulin was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or in sodium dodecyl sulfate and urea. In each instance, the initial peptide fragments were approximately 40-45K and 30K, with iodothyronine contents similar to or less than that of intact thyroglobulin. Later products of digestion than that of intact thyroglobulin. Later products of digestion included first, 20K peptides, which showed a low iodothyronine content, and finally, peptides of approximately 10K, which showed a 1.5-fold enrichment of T4 and T3 over that of intact thyroglobulin. Each of the thiol endopeptidases had a synergistic effect when incubated with cathepsin D and [125I]thyroglobulin. Among the products of such incubations were small iodopeptides, which were iodothyronine-enriched, and free T4, itself. The results show that thiol endopeptidases are present in the thyroid gland and are collectively as important as cathepsin D in the hydrolysis of thyroglobulin in vitro. The action of these enzymes must be considered along with that of cathepsin D in understanding thyroglobulin hydrolysis in vivo.
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PMID:Thyroglobulin degradation by thyroidal proteases: action of thiol endopeptidases in vitro. 704 63

The isoenzyme composition of cathepsin D from bovine hypothalamus was studied by isoelectric focusing. It was found that the soluble fraction of hypothalamic proteins contains five peaks of endopeptidase activity at pH 3.2. The properties studied allowed to identify these peaks of endopeptidase activity as isoenzyme forms of cathepsin D.
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PMID:[Isoenzyme composition of cathepsin D from bovine hypothalamus]. 721 62

Six peaks of the endopeptidase activity at pH 3.2 were obtained after isoelectric focusing of soluble fractions of cortex and hypothalamus of the human brain. The molecular weight of these endopeptidases are approximately 50000. All obtained endopeptidases possess almost the same Km and I50 relative to the substrate--pyridoxal globin and specific inhibitor--pepstatin. The studies of the revealed properties show that the endopeptidases are multiple forms of cathepsin D.
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PMID:[Multiple forms of cathepsin D from the human brain]. 732 91


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