Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O95477 (membrane-bound)
 29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostasomes are membranous vesicles (150-200 nm diameter) present in human semen. They are secreted by the prostate and contain large amounts of cholesterol, sphingomyelin and Ca2+. In addition, some of their proteins are enzymes. Prostasomes enhance the motility of ejaculated spermatozoa and are involved in a number of additional biological functions. It has been demonstrated that lipid can be transferred from prostasomes to sperm by a fusion process occurring at slightly acidic pH. In this paper, we show that an aminopeptidase activity is transferred from prostasome to sperm. This may be of particular interest since it indicates the involvement of protein in the process of fusion and because sperm may acquire new membrane-bound proteins by this procedure.
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PMID:Transfer of aminopeptidase activity from prostasomes to sperm. 930 99

1. The levels of three aminopeptidase activities involved in the degradation of enkephalins (soluble, M and MII) in several rat brain areas were studied after lidocaine administration. 2. Soluble aminopeptidase activity showed decreases in the frontal cortex and in the pituitary gland after treatment. 3. No significant changes in the complete membrane-bound aminopeptidase activity were appreciated in any other of the brain areas. 4. However, decreases of the membrane-bound puromycin-insensitive aminopeptidase activity in the frontal cortex, the hippocampus and the thalamus, after lidocaine administration, were observed.
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PMID:Effect of lidocaine administration on the enkephalin-degrading aminopeptidase activities in discrete areas of the rat brain. 937 62

The adaptive modulation hypothesis posits that the expression of digestive proteins should be modulated in response to intake of their respective substrates. A corollary of this hypothesis suggests that dietary flexibility and digestive plasticity should be correlated. We examined these two hypotheses in two granivorous Chilean birds (Zonotrichia capensis and Diuca diuca) that differ in dietary breadth. D. diuca is a strict granivore, whereas Z. capensis also eats insects. In field-caught birds, the activity of the intestinal dipeptidase aminopeptidase-N was positively correlated with intake of insects in Z. capensis but not in D. diuca. This is the first field documentation of modulation of intestinal enzymes by diet in birds. Intestinal maltase and sucrase activities were not correlated with seed (vs. insect) intake in either species. In the laboratory, captive birds of both species exhibited similar modulation of membrane-bound intestinal hydrolases when fed on synthetic diets of contrasting carbohydrate and protein composition. Maltase, sucrase, and aminopeptidase-N activities were significantly higher in birds fed on the carbohydrate-free than those on the carbohydrate-containing diet. Activities of the three enzymes were positively correlated. Therefore, this increase probably resulted from nonspecific increases of all enzymes resulting from intake of the carbohydrate-free diet. Principal components analysis separating the effect of diet on specific and on nonspecific modulation revealed that diet had a strong effect on nonspecific activity of intestinal enzymes in both Z. capensis and D. diuca. Diet also significantly affected aminopeptidase-N activities when the effect of diet on nonspecific modulation was removed. Birds fed on the carbohydrate-free, high-protein diet had significantly higher specific aminopeptidase-N activities than those fed on the carbohydrate-containing diet. Our results cast doubts on the notion that dietary flexibility and the plasticity of the gut's enzymes are necessarily correlated and on the general validity of the adaptive modulation hypothesis.
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PMID:Dietary flexibility and intestinal plasticity in birds: a field and laboratory study. 954 55

Aminopeptidase A (EC 3.4.11.7; APA) is a 130 kDa membrane-bound zinc enzyme that contains the consensus sequence HEXXH (residues 385-389) conserved among the zinc metalloprotease family. In this motif, both histidine residues and the glutamic residue were shown to be involved respectively in zinc co-ordination and catalytic activity. Treatment of APA with N-acetylimidazole results in a loss of enzymic activity; this is prevented by the competitive aminopeptidase inhibitor amastatin, suggesting the presence of an important tyrosine, lysine or cysteine residue at the active site of APA. A tyrosine residue was previously proposed to be involved in the enzymic activity of aminopeptidase N. Furthermore sequence alignment of mouse APA with other monozinc aminopeptidases indicates the presence of a conserved tyrosine (Tyr-471 in APA). The functional role of Tyr-471 in APA was investigated by replacing this residue with a phenylalanine (Phe-471) or a histidine (His-471) residue by site-directed mutagenesis. Kinetic studies showed that the Km values of both mutants were similar to that of the wild-type enzyme, whereas kcat values were decreased by three orders of magnitude and corresponded to a variation in free energy of the rate-limiting step by 4.0 and 4.2 kcal/mol (0.96 and 1.00 kJ/mol) for the Phe-471 and His-471 mutants respectively. The mutation did not modify the inhibitory potency of a thiol-containing inhibitor that strongly chelates the active-site zinc ion, whereas that of a putative analogue of the transition state presumed to mimic the reaction intermediate was reduced. Taken together, these results strongly suggest that the Tyr-471 hydroxy group participates in catalysis by stabilizing the transition state complex through interaction with the oxyanion.
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PMID:A tyrosine residue essential for catalytic activity in aminopeptidase A. 958 70

Aminopeptidase activity (AP) has been implicated in the metabolism of renal and circulating vasoactive peptides. This activity is involved in the pathogenia of hypertension, essentially in spontaneously hypertensive rats. However, no other animal models, which develop hypertension by other different ways, have been used to study the possible role of aminopeptidase activity. To investigate the role of this activity in the pathogenesis of hypertension, angiotensinase A activity (glutamyl-AP and aspartyl-AP), aminopeptidase M activity (alanyl-AP), aminopeptidase B activity (arginyl-AP), pyroglutamyl-AP, and cystinyl-AP were measured in the serum and kidney of two experimental animal models of renovascular hypertension: Goldblatt two-kidney one clip (G2K-1C) and low renal mass rats (LRM). No differences were found in serum levels of AP in LRM or G2K-1C in comparison with their respective controls. In LRM rats there was a significant decrease in membrane-bound angiotensinase A (glutamyl-AP), arginyl-AP and alanyl-AP activities. In G2K-1C rats there was a significant decrease in soluble and membrane-bound angiotensinase A activity (aspartyl-AP). Our results suggest that AP activities play a role in the regulation of renal vasoactive peptides, and respond differently depending on the cause of hypertension.
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PMID:Renal aminopeptidase activities in animal models of hypertension. 965 75

Aminopeptidase activity plays a role in the metabolism of several peptides that could be involved in blood pressure control. This activity has been implicated in the pathogenesis of hypertension, essentially in spontaneously hypertensive rats. However, few studies have examined aminopeptidase activities in animal models other than genetic hypertension. To analyze the aminopeptidase response to the specific conditions of the reduced renal mass saline model of arterial hypertension, aminopeptidase A activity (glutamyl- and aspartyl-aminopeptidase), aminopeptidase M activity (alanyl-aminopeptidase), aminopeptidase B activity (arginyl-aminopeptidase), pyroglutamyl-aminopeptidase and cystinyl-aminopeptidase were measured in the neurohypophysis, in the adrenal gland and in serum of this model of hypertension. In the neurohypophysis, there was a significant increase of soluble cystinyl-, alanyl-, arginyl-, pyroglutamyl- and membrane-bound aspartyl-aminopeptidase activities in hypertensive animals. In the adrenal gland, soluble cystinyl-, alanyl-, arginyl- and pyroglutamyl-aminopeptidase activities were also higher in hypertensive rats than in normotensive controls. No differences were found in serum levels of aminopeptidase activities between both groups of animals. A highly significant positive correlation between the neurohypophysis and the adrenal gland was observed for soluble cystinyl- and alanyl-aminopeptidase activities in the model of hypertension, whereas no correlation was observed in normotensive rats. Our results suggest that aminopeptidase activities could be involved in the regulatory response to the reduced renal mass hypertension and also suggest a coordinate response between the adrenal gland and the neurohypophysis, to the specific metabolic conditions of this model of hypertension.
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PMID:Activities of aminopeptidases in a rat saline model of volume hypertension. 966 82

Aminopeptidase A (EC 3.4.11.7, APA) is a 130 kDa membrane-bound aminopeptidase that contains the consensus sequence HEXXH (385-389) found in the zinc metalloprotease family, the zincins. Sequence alignment of the mouse APA with other monozinc-aminopeptidases indicates the presence of a highly conserved glutamate residue (Glu352 in APA) found in the conserved motif GAMEN (349-353). In monozinc-aminopeptidases, the negative charge of the glutamate side-chain carboxylate may constitute the anionic binding site involved in the recognition of the free amino group of substrates or inhibitors. The functional role of Glu352 in APA was investigated by substituting this residue with an aspartate (Asp352), a glycine (Gly352), a glutamine (Gln352) or an arginine (Arg352) residue by site-directed mutagenesis. Kinetic studies showed that the Km values of the mutant enzymes were unaffected, whereas kcat values were decreased 10-250-fold, resulting in a 10-, 30- 260- and 400-fold reduction in cleavage efficiencies for the mutants Asp352, Gly352, Gln352 and Arg352 respectively. The inhibitory potency of two different classes of inhibitors, a thiol and a phosphonate compound, was significantly (P<0.05) decreased by 10- and 4-fold respectively in the mutated enzymes. Moreover, the inhibitory potency of angiotensin I, used as a competitor of the synthetic substrate alpha-l-glutamyl beta-naphthylamide, displayed a 4-fold reduction (P<0.01) in the mutated enzymes, whereas the Ki values of its N-acetyl derivative were unchanged. These data strongly suggest that Glu352 is involved in the catalytic process of APA and contributes to the exopeptidase activity of this enzyme through interaction with the N-terminal part of substrates or inhibitors.
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PMID:A glutamate residue contributes to the exopeptidase specificity in aminopeptidase A. 971 99

The surface of most cells includes a coterie of resident proteins which act as receptors for a wide variety of ligands and other proteins which are potentially bioactive on cell-cell contact (juxtacrine effects), or else are released by enzyme activity to influence cell behaviour by autocrine or paracrine mechanisms. We previously found that UVC irradiation stimulates the release of TGFalpha from its membrane-bound preprocursor form whereby it acts as a stimulus to rapid, reparative cell multiplication; clearly this runs the risk hastening mitosis before UV-induced DNA damage is fully corrected, which in turn may increase the likelihood of residual lesions persisting and hence of new mutations being generated. We found that sublethal UVC irradiation (10 J m(-2)) of HeLa cell cultures also resulted in activation of ecto-aminopeptidase and ecto-endopeptidases which were maximal 16 and 20-24 h after irradiation, respectively. Both of these classes of protease were shown to be metalloproteases using a nonapeptide substrate (called P9) which is cognate to the N-terminal cleavage site of preproTGFalpha except for a reporter 125I-tyrosine [Piva et al., J. Cell. Biochem. 64 (1997) 353-368]. We now show that the N-terminal tyrosine cleaved from P9 by cell surface aminopeptidase activity, was found to be taken up by the cell resulting in its 10-25-fold concentration intracellularly, some two- to threefold higher than from a reservoir source, and may represent a novel salvage pathway for recovery of essential amino acids. Aminopeptidase activity was found to be both temperature- and FBS-dependent but was not reliant on ATP for its activity. Tyrosine transport across the cell membrane was also temperature and FBS-dependent but required ATP for maximal activity. UVC irradiation enhanced aminopeptidase activity but not tyrosine uptake by the cultures. The fraction of HeLa cells undergoing apoptosis increased in those cultures which were exposed to higher doses of UVC. The levels of ecto-aminopeptidase and ecto-endopeptidase activity in apoptotic cells were elevated compared to viable cells receiving the same dose of UVC. These results suggest that increased levels of cell surface protease activity in apoptotic cells would increase the amounts of free amino acids and growth factors in the extracellular medium and hence stimulate the proliferation of surrounding cells to replace those killed by UV irradiation.
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PMID:Effect of UV irradiation on cell surface protease activity and amino acid uptake. 992 Apr 28

Membrane-bound cell surface peptidases including aminopeptidase-N (EC 3.4.11.2), dipeptidyl peptidases IV (EC.3.4.14.5), carboxypeptidase-M (EC 3.4.17.12), neutral endopeptidase (EC 3.4.24.11) and endothelin converting enzyme-1 (EC 3.4.23) were shown to be differently expressed on human ovarian granulosa, theca interna and luteal cells and on endometrial epithelial and stromal cells. These peptidases have their catalytic sites extracellularly and can metabolize biologically active peptides at the cell surface, serving as local regulators of peptide concentrations. In the ovary and endometrium, numerous peptides are considered to be locally produced and play an important role in the follicular growth, ovulation, corpus luteum function, endometrial differentiation and embryo implantation in an autocrine and/or paracrine fashion. The inhibition of aminopeptidase activity by bestatin affected murine follicular growth, steroidogenesis by porcine ovarian cells and progesterone-induced decidualization of human endometrial stromal cells in vivo or in vitro. These findings suggest that membrane-bound peptidases are important regulators of the function and differentiation of the ovarian cells and endometrial cells including embryo. In the near future, the physiological roles of these peptidases will be clarified and clinical use of peptidase inhibitors may be applied to the various reproductive disorders.
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PMID:Membrane-bound cell surface peptidases in reproductive organs. 1042 64

Neonatal handling decreases neutral endopeptidase 24.11 activity in the amygdala. However, this procedure does not affect aminopeptidase activities in any of the brain areas studied. Neonatal handling has been one of the most commonly used strategies to study the plasticity of the nervous system. The crucial role of the opioids in the control of different aspects of behaviour and development has been well documented. Regarding this subject, the endogenous opioid system might mediate some of the effects induced by neonatal handling. In this work, we have studied the effects of neonatal handling on several enkephalin-degrading peptidases, including soluble and membrane-bound aminopeptidases (puromycin-sensitive and -insensitive) and neutral endopeptidase 24.11 in different rat brain areas. Tyrosine aminopeptidase activities were measured fluorimetrically using tyrosine-beta-naphthylamide as substrate and puromycin as selective inhibitor of one of the membrane-enzymes. Dansyl-D-Ala-Gly-Phe(pNO2)-Gly was the fluorogenic substrate for neutral endopeptidase. The reduced neutral endopeptidase 24.11 activity in the amygdala of neonatal handled rats could reduce enkephalin catabolism in this area and it could be responsible for some of the effects induced by neonatal handling.
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PMID:Effect of neonatal handling on brain enkephalin-degrading peptidase activities. 1051 96


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