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)

The synthetic prostaglandin 16,16-dimethyl E2 (PGE2) given by intravenous infusion at 0.4 mug/kg-h inhibited gastric secretion of H+, K+, Cl-, and pepsin in four fistula dogs stimulated by histamine (H), pentagastrin (P), urecholine (U), and 2-deoxy-D-glucose (2-DG). When given for 90 min during steady infusions of near-maximal doses of H, P, and U, PG-E2 caused 75% inhibition of H+ maximally at 90 min and over 85% inhibition of pepsin secretion maximally at 45 min. Recovery of secretion took 1-2 h after infusion of PGE2 was stopped. Injection of KCl, 1 meq/kg, during inhibition of histamine by PGE2 gave only a 15-min transient reversal in inhibition. When PGE2 was given as background to 45-min step-dose responses, 0.1 mug/kg competitively inhibited histamine stimulation and 0.4 mug/kg-h gave 100% inhibition. Against pentagastrin, 0.1 mug PGE2/kg-h had no effect and 0.4 mug caused uncompetitive inhibition; against urecholine, 0.4 mug PGE2/kg-h caused competitive inhibition of H+ secretion. Pepsin was more markedly inhibited in each case. There were no side effects at either dose of PGE2, which is a potent inhibitor of gastric secretion with all forms of stimuli.
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PMID:Inhibition of gastric secretion in the dog by 16,16-dimethyl prostaglandin E2. 0 75

Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme. In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway.
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PMID:A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney. 0 94

Pepsin was spin-labelled with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidyl) bromoacetamide, possibly at the active site, at a beta-catboxyl group of a reactive aspartic acid. The spectrum of the spin-labelled pepsin showed that the spin probe was strongly immobilized (correlation time is greater than or equal to 10(-8) sec). Spin-labelled pepsin was thermally denatured at various temperatures and electron paramagnetic resonance (e.p.r.) spectra were taken at various times. Rates of denaturation estimated from the e.p.r. spectra at various temperatures showed that the enthalpy and entropy of thermal denaturation of spin-labelled pepsin at pH 3.5 were 48.0+/-4.9 kcal/mole and 214.7+/-14.5 e.u. respectively. Addition of conc. NaOH or 1 M acetate buffer at pH 6.0 sharpened e.p.r. spectra of the spin-labelled pepsin, indicating that the spin probe became mobilized by alkaline denaturation. Addition of urea caused unfolding of the protein which increased with the urea concentration, although only slight transition of conformational changes was observed in the e.p.r. spectra.
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PMID:Electron paramagnetic resonance studies on spin-labelling of pepsin: effects of temperature, pH and urea on its conformation. 0 80

This paper presents the methods for galenical investigations of a new gastrotherapeutic preparation. The results and their possible relations to therapy are discussed. The preparation is presented a press-coated tablet. Its antacid characteristics concerning the rate of effectiveness, potency and duration are compared with leading brands on the German market. Pepsin inactivation together with the rapid liberation of the spasmolytic agent propantheline and the psychically stabilising agent peranzine are demonstrated. The results of the stability tests for the active ingredients and the in vitro availability are described. The new product is a gastrotherapeutic preparation, which fulfils all requirements for rapid action and reliable therapy.
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PMID:[Galenic studies of a new gastrotherapeutic drug]. 0 61

The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325 pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements.
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PMID:Total folate binding capacity of normal human plasma, and variations in uremia, cirrhosis, and pregnancy. 1 60

Radioactive selenite reacts with purified human and goat immunoglobulins at acidic and neutral pH. The antigenic properties of the immunoglobulins are retained during the selenium labelling as shown by immunoelectrophoresis and autoradiography. Pepsin digests of 75Se-labelled IgG possess 75Se both in the (Fab')2 fraction and in the low molecular weight peptides derived from the Fc domains. Alpha-1-acid glycoprotein, ribonuclease, and lysozyme are also labelled by this procedure. Enhancement of 75Se incorporation by urea, guanidinium chloride, mercaptoethanol, sodium sulfite and carrier selenite is interpreted as an effect of destabilization of IgG disulfide bonds. Up to 1.4 g atoms Se per mol IgG have been incorporated. We assume that selenite is cleaving disulfides by a process akin to sulfitolysis. The lability of the isolated 75Se-labelled IgG to high concentrations of mercaptans and sulfite is consistent with this idea. These 75Se-labelled proteins may be useful in structure studies and radioimmunoassay.
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PMID:Reaction of selenium with immunoglobulin molecules. 1 84

In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.
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PMID:Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. 2 30

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

1. The high oxygen affinity of fetal blood in rabbits is due to a very low concentration of 2,3-diphosphoglycerate (2,3-DPG) in the red cells. In order to gather informations on the factors responsible for this characteristic we have studied synthesis and break-down of 2,3-DPG in fetal and adult rabbit red cells in vitro and examined possible regulative pathways which may lead to the low 2,3-DPG concentration in vivo. 2. Under conditions where 2,3-DPG and 3-phosphoglycerate (3-PGA) accumulate in adult erythrocytes, i.e. in a solution containing inosine, pyruvate and inorganic phosphate, the amount of 2,3-DPG synthetized in fetal red cells was only 40% of the adult value and 3-PGA was not measurable. Upon inhibition of enolase by NaF, however, both 2,3-DPG and 3-PGA increased to a similar extent in fetal and adult red cells. These findings point towards differences in the pyruvate kinase (PK) reaction which is one of the rate limiting steps of glycolysis. Direct measurements revealed an over tenfold higher PK activity in fetal compared to adult red cells. This higher activity of PK will lead to a decreased concentration of 3-PGA with a consecutive fall in 2,3-DPG concentration. 3. Other factors, like a decreased glucose utilization, a decreased activity of 2,3-DPG mutase or an increased 2,3-DPG phosphatase activity could be excluded as a cause for the low 2,3-DPG concentration in fetal red blood cells. The same holds for extraerythrocytic factors like glucose concentration or pH value in fetal blood. 4. During the postnatal development of rabbits the PK activity decreased. 50 days after birth, PK activity was 20% of the fetal value but still somewhat higher than in adult erythrocytes. This change is paralleled by an increase in 2,3-DPG concentration and half saturation oxygen pressure. With respect to the synthesis of 2,3-DPG and ATP, the fetal rabbit red cell is comparable to hereditary high PK activity in human erythrocytes.
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PMID:High pyruvate kinase activity causes low concentration of 2,3-diphosphoglycerate in fetal rabbit red cells. 2 78

1. Of the three major human pepsins, pepsin 1 has greater proteolytic activity towards ovalbumin than has pepsin 3. Pepsin 5 has low activity towards this substrate. 2. Proteolytic pH-activity curves show only on pH maximum, about pH 1.4 for pepsin 1, pH 1.4--1.5 for pepsin 3 and pH 1.2--1.4 for pepsin 5. The curve for pepsin 3 has a shoulder between pH 2.4 and 3.4. 3. The rate of digestion of ovalbumin by pepsin 1 is approximately three times slower than are those of bovine haemoglobin or human globin. 4. The results suggest that there may be a physiological advantage in having more than one pepsin.
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PMID:Ovalbumin digestion by human pepsins 1, 3 and 5. 3 68


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