Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new type of glycopeptidase hydrolyzing beta-aspartylglycosylamine linkages was partially purified from almond emulsin by chromatography on Sephadex G-200 and DE 52. The enzyme degraded stem bromelain glycopeptide, Asn-Asn(Man3,Xyl1,Fuc1,GlcNAc2)-Glu-Ser-Ser, to yield equimolar amounts of intact oligosaccharide, peptide (Asn-Asp-Glu-Ser-Ser), and ammonia. The Km value for the stem bromelain glycopeptide was 4 mM, and the optimum pH was 5.2. The enzyme was markedly inhibited by 10 mM Cu2+, Fe3+, and Zn2+. Thiol inhibitors and actinomycete protease inhibitors had no effect. The glycopeptides used as substrates were prepared from stem bromelain, ovalbumin or ovotransferrin. The enzyme hydrolyzed glycopeptides with 3-11 amino acid residues, whereas it did not hydrolyze glycopeptides with 1-2 amino acid residues. Furthermore, Asn-oligosaccharide was not inhibitory to the enzyme.
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PMID:Some characteristics of a new glycopeptidase acting on aspartylglycosylamine linkages. 73 97

Intact dipeptidyl aminopeptidase IV (DAP IV) was solubilized by bromelain treatment from human kidney brush border plasma-membranes. Purification of DAP IV was performed by a 3-step method, applying lectin-affinity chromatography on WGA-Sepharose, gel filtration and anion-exchange chromatography. DAP IV from human kidney cortex showed a pH optimum of 8.7 and was totally inhibited by 1 mmol/l Zn2+. Isolated DAP IV revealed a relative molecular mass of 250 kDa as determined by the native-PAGE method and of 220 kDa by the gel filtration method. Analytical isoelectric focussing of DAP IV revealed an isoelectric point of pH 5.3. Ultrastructural analysis of isolated DAP IV fractions, using the negative staining technique, disclosed the presence of numerous globular particles with an average diameter of 5 nm which correspond to the structural substrate of the purified protein.
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PMID:Isolation and characterization of dipeptidyl aminopeptidase IV from human kidney cortex. 256 59

A new method for removing nearly all active endoproteinases from fluids called "sandwich affinity chromatography" is described. It is based on strong chelate binding of alpha 2-macroglobulin (alpha 2M) and its proteinase complexes to Zn2+-bis-carboxymethylamino-Sepharose (Zn chelate-Sepharose) and its ability to complex most active endoproteinases. The preferred performance minimizing unspecific protein adsorption is binding first alpha 2M to Zn chelate-Sepharose and then adsorbing the proteinase to the alpha 2M-Zn chelate-Sepharose using elevated salt concentrations. A suitable standard buffer, in which most proteases and alpha 2M are active and the protease-alpha 2M complex remains bound to Zn chelate-Sepharose, is 0.02 mol/liter sodium phosphate, pH 6.5, containing 0.15 mol/liter NaCl. As an example, the reaction of trypsin with alpha 2M-Zn chelate-Sepharose was studied. After saturating Zn chelate-Sepharose first with alpha 2M and then with trypsin under standard conditions, the bound alpha 2M equals the bound trypsin activity (measured with Chromozym TRY). The specific binding capacity of alpha 2M-Zn chelate-Sepharose for proteases was determined in this way to be 30-40 U trypsin, i.e., 0.40-0.54 mg/ml of gel. The balance and the fact that the bound trypsin is inaccessible to soybean trypsin inhibitor indicate that at these conditions no unspecific trypsin binding occurs. Chymotrypsin, thermolysin, elastase, bromelain, ficin, and papain are also bound at standard conditions but not exoproteases like carboxypeptidases A and Y. Advantages of the sandwich affinity chromatography are the simple loading procedure by adsorption, the high capacity of the gel material, and the possibility to reuse the Zn chelate-Sepharose after eluting reacted alpha 2M and reloading with new alpha 2M.
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PMID:Removal of endoproteinases from biological fluids by "sandwich affinity chromatography" with alpha 2-macroglobulin bound to zinc chelate-Sepharose. 620 48

The ratio of kininogen that is substrate of plasma kallikrein to kininogen, which is not substrate of plasma kallikrein in canine plasma, was about 1:3.6 by differential assay of kininogens. When the plasma was gel-filtered through a column of Sephacryl S-300 superfine, two fractions, which released kinin by trypsin, were obtained. These results indicate that two kininogens with different molecular weights are present in the plasma and they show different susceptibility to plasma kallikrein. One kininogen was purified by ion-exchange and zinc-chelating affinity chromatographies. Purified kininogen showed a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing condition and its molecular weight was 125 kDa. Released kinin from the kininogen by trypsin was bradykinin. The kininogen inhibited papain and ficin but did not inhibit bromelain at the concentration used. The kininogen bound to carboxymethylated-papain and this binding was dissociated by 3M NaSCN. Canine plasma shortened the abnormal clotting time of human high molecular weight kininogen-deficint plasma. The kininogen also shortened the abnormal clotting time of the plasma. From these results, the purified kininogen was high molecular weight kininogen and it was multi-functional protein.
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PMID:Canine plasma kininogen: evidence for the presence of two kininogens and purification of high molecular weight kininogen and characterization as multi-functional molecule. 929 98

The purpose of this review was to search the scientific literature for dietary compounds that alleviate or exacerbate symptoms of lupus erythematosus (LE) in both animal and human models. A detailed literature review was undertaken to find articles showing a relationship between LE and nutrition by using MEDLINE/INDEX MEDICUS (1950-March 2000) for English-language articles, followed by cross-referencing. Aggravating substances appear to include excess calories, excess protein, high fat (especially saturated and omega-6 polyunsaturated fatty acids), zinc, iron, and L-canavanine found in alfalfa tablets. Possible beneficial dietary compounds include vitamin E, vitamin A (beta-carotene), selenium, fish oils (omega-3 polyunsaturated fatty acids), evening primrose oil, flaxseed, a plant herb (Tripterygium wilfordii), dehydroepiandrosterone, and calcium plus vitamin D (if taking corticosteroids). Some people with systemic LE placed on food allergy elimination diets reported improvement in their LE symptoms; however, this may be related to a decrease of other substances in the diet. Also, although no direct evidence was reported on the beneficial effects of either bromelain or a vegetarian diet (possibly allowing fish), it is suggested that they might be beneficial. Limitations to this research are that the findings are based on relatively few studies, many of which were without control groups or extrapolated from animal models. No large-scale studies have been performed with LE patients to substantiate the benefit, if any, of these individual dietary interventions, and if they were conducted, the remission and exacerbation pattern of LE may interfere with elucidating their effectiveness. Also, dietary changes should not be attempted without a physician's approval/monitoring.
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PMID:Lupus erythematosus and nutrition: a review of the literature. 1107 Jan 44

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
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PMID:Small bowel review: normal physiology part 1. 1176 47

Patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions, and fruits and vegetables (at least five servings a day). Physicians may need to be more cautious when prescribing antibiotics to children in their first year of life when they are born to families with a history of atopy. More research is needed to establish whether supplementation with probiotics (lactobacillus and bifidobacterium) during the first year of life or after antibiotic use decreases the risk of developing asthma and allergic rhinitis. Despite a theoretic basis for the use of vitamin C supplements in asthmatic patients, the evidence is still equivocal, and long-term studies are needed. The evidence is stronger for exercise-induced asthma, in which the use of vitamin C supplementation at a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma. Long-term studies of fish oil and vitamin C are needed for more definite answers. For the patient interested in incorporating nutritional approaches, vitamin C and fish oils have a safe profile. However, aspirin-sensitive individuals should avoid fish oils, and red blood cell magnesium levels may help in making the decision whether to use additional magnesium supplements. Combination herbal formulas should be used in the treatment of asthma with medical supervision and in collaboration with an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia and gingko, may be used singly as adjuncts to a comprehensive plan of care if the patient and practitioner have an interest in trying them while staying alert for drug-herb interactions. No data on the long-term use of these single herbs in asthma exist. For the motivated patient, mind-body interventions such as yoga, hypnosis, and biofeedback-assisted relaxation and breathing exercises are beneficial for stress reduction in general and may be helpful in further controlling asthma. Encouraging parents to learn how to massage their asthmatic children may appeal to some parents and provide benefits for parents and children alike. Acupuncture and chiropractic treatment cannot be recommended at this time, although some patients may derive benefit because of the placebo effect. For patients with allergic rhinitis, there are no good clinical research data on the use of quercetin and vitamin C. Similarly, freeze-dried stinging nettle leaves may be tried, but the applicable research evidence also is poor. Further studies are needed to assess the efficacy of these supplements and herbs. Homeopathic remedies based on extreme dilutions of the allergen may be beneficial in allergic rhinitis but require collaboration with an experienced homeopath. There are no research data on constitutional homeopathic approaches to asthma and allergic rhinitis. Patients with COPD are helped by exercise, pulmonary rehabilitation, and increased caloric protein and fat intake. Vitamin C and n-3 supplements are safe and reasonable; however, studies are needed to establish their efficacy in COPD. On the other hand, there are convincing data in favor of N-acetyl-cysteine supplementation for the patient with COPD at doses ranging between 400 and 1200 mg daily. Red blood cell magnesium levels may guide the use of magnesium replacement. The use of L-carnitine and coenzyme Q10 in patients with COPD needs further study. The addition of essential oils to the dietary regimen of patients with chronic bronchitis is worth exploring. Patients with upper respiratory tract infections can expect a shorter duration of symptoms by taking high doses of vitamin C (2 g) with zinc supplements, preferably the nasal zinc gel, at the onset of their symptoms. Adding an herb such as echinacea or Andrographis shortens the duration of the common cold. The one study on Elderberry's use for the flu was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting, but more studies should be performed. Saline washes may be helpful to patients with allergic rhinitis and chronic sinusitis. Patients also may try the German combination (available in the United States) of elderberry, vervain, gentian, primrose, and sorrel that has been tested in randomized clinical trials. Bromelain is safe to try; the trials of bromelain supplementation were promising but were never repeated. The preceding suggestions need to be grounded in a program based on optimal medical management. Patients need to be well educated in the proper medical management of their disease and skilled at monitoring disease stability and progress. Asthmatic patients need to monitor their bronchodilator usage and peak flow meter measurements to step up their medical treatment in a timely manner, if needed. Patients welcome physician guidance when exploring the breadth of treatments available today. A true patient-physician partnership is always empowering to patients who are serious about regaining their function and health.
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PMID:Respiratory and allergic diseases: from upper respiratory tract infections to asthma. 1239 10

An inhibitor of the metallo-ectoenzyme, pyroglutamyl aminopeptidase II (PPII), a thyrotropin releasing hormone-specific peptidase, was identified by screening extracts from marine species of the Cuban coast-line belonging to the phylla Chordata, Echinodermata, Annelida, Mollusca, Cnidaria, Porifera, Chlorophyta and Magnoliophyta. Isolation of the inhibitor (HcPI), from the marine annelide Hermodice carunculata, was achieved by trichloroacetic acid treatment of the aqueous extract, followed by ion-exchange chromatography on DEAE Sephacel, gel filtration on Sephadex G-25 and reverse phase-HPLC. HcPI had a small apparent molecular weight (below 1000 Da) and was not a peptide. It inhibited rat PPII (a membrane preparation with 8.5mg protein/ml) with an apparent K(i) of 51 nM. HcPI did not inhibit serine (trypsin, chymotrypsin, elastase and dipeptidyl aminopeptidase IV), cysteine (papain, bromelain and pyroglutamyl aminopeptidase I), aspartic (pepsin and recombinant human immunodeficiency virus 1 protease (HIV1-PR)) nor other metallo proteinases (collagenase, gelatinase, angiotensin converting enzyme, aminopeptidase N and carboxypeptidase A). HcPI was non-toxic and active in vivo. Intraperitoneal injection of HcPI reduced mouse pituitary and brain PPII activity. Potency of the effect was higher in hypophysis and hypothalamus than in other brain regions. Intrathecal administration to male rats reduced PPII activity in the spinal cord. In conclusion we have identified a specific inhibitor of PPII that is the first M1 family zinc metallo-peptidase inhibitor isolated from marine invertebrates. It may be useful for elucidating the in vivo role of PPII in the pituitary and central nervous system.
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PMID:Purification of a specific inhibitor of pyroglutamyl aminopeptidase II from the marine annelide Hermodice carunculata. in vivo effects in rodent brain. 1459 39

Treatment of gastrointestinal infections continues to be complicated by expanding resistance to antibiotics. This has led to both new antibiotic treatments and to research on alternative therapies. In the case of Clostridium difficile colitis, interesting preliminary results have been obtained with both probiotic therapy and passive immunization strategies. The newer macrolides were found to be effective for multidrug-resistant Salmonella typhi and safe in the pediatric population. The efficacy of rifaximin, a nonabsorbed antimicrobial agent, was demonstrated in the treatment of travelers diarrhea in Mexico. The benefit of the proteolytic agent bromelain, which degrades enterocyte receptors for enterotoxigenic Escherichia coli, was shown in an experimental model of piglets challenged with this infection after bromelain prophylaxis. The potential value of zinc supplementation in infant diarrhea was shown in a study in India. The recently approved rotavirus vaccine is being withheld because of multiple reported cases of intussusception. Cryptosporidiosis continues to challenge old and new chemotherapeutic agents. The usefulness of paromomycin in Cryptosporidium infection was shown in both murine and piglet models. The cost effectiveness of prophylaxis for parasitosis in immigrants has been an area of investigation.
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PMID:Treatment of gastrointestinal infections. 1702 16

Nutrition plays a key role in optimizing healing following surgery. The increased catabolic state postoperatively, coupled with a propensity for patients to be suffering from marginal nutritional deficiencies at baseline preoperatively, necessitates that the surgeon be attuned to the need for optimal perioperative nutritional support. This ensures the smoothest recovery and best possible outcomes in facial plastic surgery. Key nutrients include vitamin A, vitamin C, zinc, bromelain, arnica montana, arginine, glutamine, hydrolyzed collagen, vitamin B complex, and protein. The ability for patients to obtain this optimal supplementation in a single product is the ideal solution for both surgeon and patient.
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PMID:The Critical Role of Nutrition in Facial Plastic Surgery. 3128 Aug 54


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