Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Large quantities of the low-molecular-weight natriuretic material (F4), which appears after the salts when fractionated on G-25 Sephadex column, were obtained from the urine of normal man on a normal diet. The natriuretic substance in F4 was (1) untrafiltrable through a membrane with a claimed molecular-weight cut-off of 500 daltons (Amicon UMO5); (2) soluble in more polar organic solvents; (3) totally soluble in 95% acetone when specific activity was doubled; (4) relatively resistant to heating at 100 degrees C for 1 hour at a pH of 10, and to heating at 110 degrees C in 6 N hydrochloric acid for up to 90 hours under anaerobic conditions, and treatment with nitrous acid; it was less resistant to these procedures when extracted into 95% acetone; (5) not destroyed by trypsin, chymotrypsin, pronase, pepsin, leucine aminopeptidase, and subtilysin, nor was it destroyed by pepsin, leucine aminopeptidase, subtilysin, carboxypeptidase A and B, and aminopeptidase M, or by monoamine oxidase, aryl sulphatase, and beta-glucuronidase when extracted into 95% acetone. The natriuretic substance in the 95% acetone-soluble F4 was totally destroyed by incubation with prolidase. The least amount of 95% acetone-soluble F4 required to produce a significant natriuresis in the bioassay rat was that derived from a 7-min sample of urine. The maximal response was obtained from a 30-min sample of urine. Continuous i.v. infusion of the 95% acetone-soluble F4 for 40 min produced a sustained natriuresis, whereas a greater amount injected as a bolus produced an effect which was not sustained beyond 20 min.
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PMID:Further observations on a low-molecular-weight natriuretic substance in the urine of normal man. 4 87

[Asn A21]Insulin is formed as the main product during alkaline saponification of insulin hexamethyl ester. Purification was achieved by gel chromatography followed by ion-exchange chromatography on carboxymethyl cellulose at pH 4 or by preparative isoelectric focusing in a granulated gel over a narrow pH range. Two main products could be isolated. One of them showed the electrophoretic behaviour of insulin (A), whilst the other corresponded to insulin with a blocked carboxyl function (B). Incubation of this product B with carboxypeptidase A liberated only the C-terminal alanine of the B-chain, but not the asparagine of the C-terminus of the A-chain. Chymotryptic digestion of the isolated S-sulfonate A-chain derivative (C) followed by high-voltage electrophoresis confirmed that the carboxyl function of asparagine A21 was blocked. In order to determine the free carboxyl functions of the A-chain derivative C, it was coupled with glycine methyl ester yielding D. Amino acid analysis of the chymotryptic peptides of D showed that the carboxyl functions of glutamic acid A4 and A17 had been free prior to coupling. The amino acid analysis of the enzymatic hydrolysate (subtilisin, aminopeptidase M) of the A-chain derivative C showed an additional peak with an elution position identical to the model compound aminosuccinimide. The biological activity of the [Asm A21[insulin was found to be about 40% in the fat cell test and 13.2 units/mg measured by the mouse convulsion method.
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PMID:[A21-Asparaginimide] insulin. Saponification of insulin hexamethyl ester, I. 83 63

Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe-Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A.
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PMID:Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase). 152 Feb 71

Sequence analysis of aminopeptidase N has shown that this zinc exopeptidase contains a consensus sequence (Val-Xaa-Xaa-His-Glu-Xaa-Xaa-His), generally found at the active site of zinc endopeptidases [Jongeneel, C. V., Bouvier, J. and Bairoch, A. (1989) FEBS Lett. 242, 211-214]. This suggests that the active site of aminopeptidase N may be closer to that of a classical zinc endopeptidase, such as thermolysin, than to that of an exopeptidase, such as carboxypeptidase A, which does not contain the above sequence. However, the nature of the other amino acids involved in the enzymatic activity of the eukaryotic aminopeptidase N remains unknown. Chemical modifying agents have now been used to characterize the active site of aminopeptidase N further. The location of the modified residues was also determined by comparing the protection given by three competitive inhibitors which interact with different subsites of the active site. Aminopeptidase N was rapidly inactivated by 2,3-butanedione and diethylpyrocarbonate and partially inactivated by N-acetylimidazole, diazoacetamide and a soluble carbodiimide, suggesting the presence of functional arginyl, histidyl, tyrosyl and aspartyl/glutamyl residues. In each case the reaction kinetics showed that the inactivation could be correlated with modification of a single residue. The protection experiments indicated that the residues are at the active site of the enzyme and that the arginine and tyrosine are probably located in the S'1-S'2 subsites, histidine in the S1 subsite and the acidic residue near the zinc binding site and the S'1 subsite. Steady-state kinetics showed that the arginine, histidine and acidic residues are involved in substrate binding, while the tyrosine may play a role in the catalytic process. All these data support an endopeptidase-like structure for the active site of aminopeptidase N.
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PMID:Functional residues at the active site of aminopeptidase N. 167 19

A fully automated exopeptidase digestion procedure for the partial determination of N- and C-terminal peptide/protein sequence is described. The digestion of various substrates with aminopeptidase M, carboxypeptidase A, P or Y was accomplished with the Varian 9090 autosampler's robotic automix routines. The released free amino acids, in addition to free amino acids from acid hydrolysates, were derivatized with phenylisothiocyanate in an automated fashion and subsequently chromatographed on a C18 column for separation and quantitation. The advantages of automating this precolumn phenylisothiocyanate derivatization are the virtual elimination of sample manipulation errors and very reproducible data due to the precise control of the reaction conditions both of which, facilitate the interpretation of the exopeptidase reaction kinetic data.
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PMID:Automated phenylthiocarbamyl amino acid analysis of carboxypeptidase/aminopeptidase digests and acid hydrolysates. 205 Jul 78

A summary is given of experiments performed to study the effects of Maillard reaction products on protein digestion and uptake. A double-isotope technique was used to evaluate the impact of compounds formed in the Maillard reaction on the intestinal uptake of dietary proteins in rats. It was found that low-molecular weight compounds from a glucose-lysine reaction mixture reduced the plasma level of dietary protein-derived lysine. The reaction mixture inhibited in vitro carboxy-peptidase A (E.C. 3.4.17.1) and the brush border enzyme aminopeptidase N (E.C. 3.4.11.2). A glucose-lysine reaction compound, 2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine was found to be a strong competitive inhibitor of aminopeptidase N (Ki = 0.2mM) in vitro. When given to rats (3 mg/g diet), it reduced the plasma level of lysine derived from both dietary free and protein-bound lysine. This compound also inhibited carboxypeptidase A, as did a number of substituted furans and pyrroles.
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PMID:Effect of Maillard reaction products on protein digestion. 250 64

Acid hydrolysis of trichloroacetic acid precipitate from rat tissue (liver, kidney and testis) homogenate released significant amounts of acid-insoluble putrescine, spermidine and spermine. Following incubation of liver homogenate with [1,4-14C]putrescine, 1.4% of total radioactivity and 1.0% of labelled diamine were recovered in the acid-insoluble fraction. Exhaustive digestion of acid-precipitable material with proteinases (Pronase, aminopeptidase M, carboxypeptidase A, B and Y) revealed the presence of di- and polyamines and of N1-(gamma-glutamyl)spermidine, N1-(gamma-glutamyl)spermine and N1,N12-bis(gamma-glutamyl)spermine. These derivatives were identified both by chromatographic analysis and by enzymatic digestion with purified gamma-glutamylamine cyclotransferase. The finding of di- and polyamine gamma-glutamyl derivatives in the proteinase-digested acid-insoluble fraction of homogenate may be considered as a proof of the in vivo transglutaminase-catalyzed binding of polyamines to proteins. This evidence suggests that di- and polyamines might have an important role in mammalian tissues through covalent binding to proteins by either one or both the primary amino groups.
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PMID:Presence of di- and polyamines covalently bound to protein in rat liver. 286 56

L-Leucinthiol, a synthetic derivative of mercaptoethylamine with a hydrophobic side chain, was recently reported to be a potent inhibitor of microsomal aminopeptidase. The structural features necessary for interaction of mercaptoamines with this enzyme have now been explored more systematically. Optimal binding requires a primary amine linked to the mercapto group via two carbon atoms. Only a substituent with L-configuration at the 1 position increased the affinity toward the enzyme. The high degree of specificity and other evidence suggest that the mode of binding of these inhibitors is similar to that of substrates. Comparison of leucinthiol with other amino compounds suggest that the mercapto group makes a much greater contribution to the binding than the hydrophobic side chain. L-Leucinthiol is fairly specific for aminopeptidase although some inhibition of thermolysin and carboxypeptidase A is observed.
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PMID:Structural requirements for specific inhibition of microsomal aminopeptidase by mercaptoamines. 400 71

p6gestibility by proteolytic enzymes of peptides cross-linked by ionizing radiation was investigated. Small peptides of alanine and phenylalanine were chosen as model compounds and aminopeptidases and carboxypeptidases were used as proteolytic enzymes. Peptides exposed to gamma-radiation in aqueous solution were analysed by high-performance liquid chromatography before and after hydrolysis by aminopeptidase M, leucine aminopeptidase, carboxypeptidase A and carboxypeptidase Y. The results obtained clearly demonstrate the different actions of these enzymes on cross-linked aliphatic and aromatic peptides. Peptide bonds of cross-linked dipeptides of alanine were completely resistant to enzymatic hydrolysis whereas the enzymes, except for carboxypeptidase Y, cleaved all peptide bonds of cross-linked peptides of phenylalanine. The actions of the enzymes on these particular compounds are discussed in detail.
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PMID:Enzymatic digestibility of peptides cross-linked by ionizing radiation. 614 37

Interrelationships between the catalytic behavior of glucose-6-phosphatase and the structure of rat-liver microsomal membranes were investigated. 2. Rabbit anti-microsomal serum completely inhibited glucose-6-phosphate hydrolysis in detergent-modified microsomes but showed no inhibitory effect on the enzyme activity of intact or mechanically disrupted vesicles. 2. Controlled proteolysis of intact microsomes using carboxypeptidase A and/or aminopeptidase M largely denatured enzymes situated on the outer surface of the microsomal vesicles such as monodehydroascorbate reductase and cytochrome c reductase. However, it did not affect the glucose-6-phosphatase activity at all, which remained in a latent state within the membrane. 3. Temperature studies on glucose-6-phosphatase have revealed that only the enzyme activity of intact microsomes exhibited a nonlinear Arrhenius plot, whereas detergent-modified microsomes showed a linear temperature response. 4. Treatment of microsomes with phospholipase C and toluene-2,4-diisocyanate resulted in an apparent loss of about 65% and 85% of the original glucose-6-phosphatase activity and was closely correlated with hydrolysis and chemical modification of phosphatidylethanolamine, respectively. These apparent inactivations could be reversed by addition of Triton X-114 alone without any phospholipid supplementation. These observations indicate that glucose-6-phosphatase is buried within the microsomal membrane, not exposed on either side. They also suggest that phospholipids are involved in the glucose-6-phosphate transport mechanism.
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PMID:Investigations on the possible involvement of phospholipids in the glucose-6-phosphate transport system of rat-liver microsomal glucose-6-phosphatase. 624 79


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