Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.
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PMID:Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. 2 56

The procedure for preparing highly purfied pepsin by chromatography on silicon dioxide with attached aminogroups (aminosilochrome) has been devised. Pepsin is eluated step=by-step: 0.0025 M and 0.05 M HCl. Results of disc-electrophoresis of purified pepsin bive evidence that the resultant preparation contains no admixtures. The activity of purified pepsin is 69 units per mg.
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PMID:[Preparation of highly puried pepsin by aminosilichrome chromatography]. 17 69

Ribulose-diphosphate carboxylase from Thiobacillus novellus has been purified to hemogeneity as observed by polyacrylamide gel electrophoresis and U.V. light observation during sedimentation velocity analysis. The optimum pH for the enzyme with Tris-HCl buffers was about 8.2. Concentrations of this buffer in excess of 80 mM were inhibitory. The apparent Km for RuDP was about 14.8 muM with a Hill value of 1.5, for HCO3- the apparent Km was about 11.7 mM with an n value of 1.18 and for Mg2+ about 0.61 mM. The enzyme was specific for this cation. Relatively high concentrations of either Hg2+ or pCMB were required before significant inhibition was observed. Activity declined slowly during a 4-hr incubation period in either 3.0 M or 8.0 M urea. Incubation for 12 hrs resulted in complete loss of activity which was not prevented by 10 mM Mg2+ and was not reversed by dialysis and subsequent addition of 10 mM cysteine. Polyacrylamide gel electrophoresis revealed a loss of the major band and the appearance of 2 new bands. SDS polyacrylamide gel electrophoresis gave an average M.W. of 73500 +/- 2500 for the slower moving band and 12250 +/- 2500 for the faster moving. However, incubation in urea for up to 40 hrs revealed a decrease in the M.W. of the slower moving band to about 60000. The Ea for the enzyme was calculated to be about 18.85 kcal mole-1, with the possibility of a "break" between 40 and 50 degrees C. The Q10 was 3.07 between 20 and 30 degrees C whereas between 30 to 40 degrees C it was 3.31. Only phosphorylated compounds caused significant inhibition of enzyme activity. They included ADP, FDP, F6P, G6P, PEP, 6PG, 2-PGA, R1P, R5P, and Ru5p.
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PMID:Properties and regulation of ribulose diphosphate carboxylase from Thiobacillus novellus. 24 94

The effect of representative agents of three classes of antisecretory compounds; prostaglandins, histamine H2-receptor antagonist, and anticholinergic agents, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg) plus HCl (150 mM) in the pylorus-ligated rat was studied. Acid was given exogenously so as to negate any antisecretory effect of the drugs studied. Both nonantisecretory and antisecretory doses of each agent as determined by preliminary secretory studies were employed. The postaglandin analogue 16,16-dimethyl prostaglandin E2, the H2-receptor antagonist cimetidine, and the anticholinergic agent probanthine, in both doses studied, all significantly reduced lesion formation. The H1-receptor antagonist mepyramine neither protected by itself nor enhanced the protective effect of cimetidine. Pepsin release into the gastric content increased with increasing mucosal damage. However, addition of pepsin to the gastric instillate had no effect on severity lesions in any group, which indicates that the increased pepsin was the result of, and not the cause of, the mucosal damage. The findings indicate that all three classes of antisecretory agents studied are also cytoprotective, i.e., they can protect against gastric mucosal injury by topical aspirin plus HCl by some mechanism other than inhibition of acid and pepsin secretion.
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PMID:Topical aspirin plus HCl gastric lesions in the rat. Cytoprotective effect of prostaglandin, cimetidine, and probanthine. 36 95

Albumin magnetic microparticles reversibly adsorb thyroxine. They quickly establish equilibrium allowing time and temperature independent measurements in T4 radioassays. We used these particles to compare the efficiency of NaOH, HCl, pepsin, sodium trichloroacetate, and 8-anilino-1-naphthalene sulfonic acid to release 125I-T4 from serum, T4-free serum and human serum albumin. We found that the efficiency of the reagents to extract 125I-T4 depended on the concentration and type of proteins to which the labelled hormone was bound. Pepsin was the most effective reagent and we utilized it for a T4 radioimmunoassay, in which albumin magnetic microparticles were used to separate free from bound hormone. We also utilized the particles in a T4 non-immune radioassay. Both assays accurately measured total serum T4, however the radioimmunoassay was simpler, less dependent on protein content of serum, required a smaller serum sample and provided slightly higher T4 values. We describe a magnetic rack which allows simultaneous handling of fifty individual tubes with an intra-assay C.V. of 2.1% for the radioimmunoassay and 2.3% for the non-immune assay and an inter-assay C.V. of 3.1%, respectively.
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PMID:Immune and non-immune T4 radioassays utilizing albumin magnetic microparticles. 63 18

Human nucleus pulposus and annulus fibrosus, obtained at autopsy from patients 7-30 years of age, were extracted with 2 M guanidine-HCl (pH 5.82) to remove proteoglycans, then stirred with pepsin in 0.5 M acetic acid, followed by three 24-h extractions with 1 M NaCl (pH 7.5) and one 24-h extraction with 2 M KSCN (potassium thiocyanate) (pH 7.2). Pepsin and NaCl solubilized an average of about 30% of nucleus pulposus collagen and 18% of annulus fibrosus collagen. KSCN extracted a further 34% of nucleus pulposus collagen and only 4% of annulus fibrosus collagen. CM-cellulose chromatography of nucleus and annulus collagen purified from the pepsin, NaCl and KSCN supernatants consistently revealed only one peak, always appearing slightly ahead of the alpha1 position for rat tail tendon type I collagen. Polyacrylamide and SDS-gel electrophoresis consistently revealed only one band with the mobility of alpha1 chains. Amino acid composition of collagen from nucleus and annulus is comparable to those of mammalian and avian cartilage type II collagen, and distinctly different from those of rat tail tendonand guinea pig skin type I collagens. Periodate oxidation of nucleus and annulus collagens showed that 81% and 67%, respectively, of the hydroxylysine residues survive treatment, compared to 71% for bovine articular cartilage collagen and 17% for guinea pig skin collagen. Total hexose analysis revealed 1.8 muM and 2.0 muM hexose per muM periodate-stable hydroxylysine in nucleus and annulus collagens, respectively. Ion exchange chromatography showed the presence of glucose and galactose in a ratio of 0.92:1 in nucleas collagen and 1.07:1 in annulus collagen. Pepsin-solubilized, NaCl-extracted collagen from nucleus and annulus formed native-type fibrils in vitro. The banding patterns of ATP-induced segment-long-spacing precipitates of nucleus and annulus collagens were identical to each other and indistinguishable from those of cartilage (type II) collagen, but distinctly different from those of rat tail tendon (type I) collagen. These data suggest that the collagen which can be extracted after limited pepsin attack of human nucleus and annulus is of the form [alpha1 (II)]3.
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PMID:Pepsin-solubilized collagen of human nucleus pulposus and annulus fibrosus. 78 25

Pepsin secretion is stimulated by the back-diffusion of acid across the mucosa of the vagally denervated canine pouch. If back-diffusion is enhanced by damage, pepsin secretion increases. The current study investigates whether this mechanism exists in man. The stomach of normal human volunteers were irrigated for 1 hour with either buffer of 0.01 N HCl, 1 hour with 0.2 N HCl, and a final hour with buffer or 0.01 N HCl. During the middle hour both the concentration and output of pepsin increased three- or fourfold. From these studies it appears that the human gastric mucosa contains a mechanism similar to the dog's which results in the stimulation of pepsin secretion when exposed to acid. This mechanism could be of etiologic significance in gastric ulcer disease, which has been shown to be associated with increased gastric-mucosal permeability.
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PMID:Stimulation of human pepsin output by tropical hydrochloric acid. 109 97

The effect of mucoadhesive polymeric vehicles on the mydriatic efficacy, and on the systemic and ocular absorption of cyclopentolate from eyedrops was studied in albino rabbits. Combining cyclopentolate base to polygalacturonic (CY-PGA) or hyaluronic (CY-HA) acid resulted in an increased mydriatic effect when compared with cyclopentolate hydrochloride (CY-HCl). During the first half an hour, the systemic absorption of cyclopentolate was lower after CY-PGA than after CY-HCl. The ocular penetration of cyclopentolate, based on drug concentrations in aqueous humor 30 minutes after the eyedrop instillation, was increased 3 fold when the polygalacturonate complex was used. CY-PGA, as well as other polymeric salts, might offer a possibility to increase the therapeutic index of cyclopentolate.
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PMID:The effect of some macromolecular ionic complexes on the pharmacokinetics and -dynamics of ocular cyclopentolate in rabbits. 140 95

Studies were conducted with four (50 to 70 kg) barrows to evaluate the mobile nylon bag technique (MNBT) for determining the apparent protein digestibility (AD) in a variety of feedstuffs. One-gram samples of each feedstuff, ground through a 1.0-mm mesh screen, were enclosed in nylon bags (25 X 40 mm; 48 microns mesh). Following predigestion (.01 N HCl; 4,000 Folin Intestinal Pepsin Units/liter), four bags of each sample were inserted into each pig via a duodenal T-cannula. The indigested contents were pooled within pig and feedstuff prior to crude protein analysis. The AD of each feedstuff was determined previously with four barrows according to the conventional method (CM), based on a 5-d total collection of feces following a 14-d adaptation period. The following results, AD (%), were obtained with the MNBT (n = 4) and CM (n = 4), respectively. Barley, 70.1 vs 81.2 (P less than .05); corn, 72.3 vs 82.1 (P less than .05); wheat, 79.6 vs 86.4 (P less than .05); corn gluten feed, 73.9 vs 70.9; rice bran, 57.3 vs 57.4; wheat middlings, 70.8 vs 79.4 (P less than .05); soybean meal, 89.9 vs 93.0; a mixture of soybean meal and hulls, 86.9 vs 88.8; coconut expeller, 65.0 vs 69.8; fababeans, 79.5 vs 78.5; peas, 87.6 vs 88.1; meat meal, 83.2 vs 84.0; complete diet (4.3% crude fiber), 76.3 vs 83.6 (P less than .05); and complete diet (13.6% crude fiber), 56.5 vs 55.0.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The evaluation of the mobile nylon bag technique for determining the apparent protein digestibility in a wide variety of feedstuffs for pigs. 270 43

The low-molecular-mass surfactant protein fraction, soluble in chloroform/methanol, contains at least two separate polypeptide chains. The 8-kDa form (type I) was isolated, [14C]carboxymethylated after reduction, and submitted to structural analysis. Its highly hydrophobic nature complicated purification, proteolytic cleavages, and sequence analysis. Acid hydrolysis in 6 M HCl for 7 days was necessary for release of branched-chain residues in full yield. Pepsin was the only enzyme found to cleave the surfactant protein and was used to complement peptide generation by chemical cleavage with CNBr. The primary structure deduced consists of 79 residues with 8 half-cystine residues, and a total of 39% branched-chain hydrophobic residues. However, 11 residues are charged at physiological pH, and all properties of the primary structure are not entirely outstanding in relation to those of other proteins. Hydrophobic segments, coupled with a presumably tight folding from the presence of disulfide bridges, probably explain the unusual properties and the solubility in organic solvents.
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PMID:Low-molecular-mass surfactant protein type 1. The primary structure of a hydrophobic 8-kDa polypeptide with eight half-cystine residues. 335 11


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