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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The range of activity and the location of lipase and pepsin were determined in the stomach and duodenum of infants, children, and adults. The range of lipase activity in biopsy specimens from the gastric body, in 29 subjects aged from 3 months to 26 years, was 1.8-5.3 U/mg protein (1 U is 1 mumol [3H]oleic acid released from tri-[3H]olein per minute). There were no significant differences among age groups (5-19 months, 2-4 years, 6-10 years, 11-13 years, and 15-26 years). Lipase activity was low or undetectable in the gastric antrum of all subjects. Pepsin activity in specimens from the gastric body ranged from 180 to 780 pepsin units/mg protein (using hemoglobin as substrate). The antrum had significantly lower pepsin activity (P less than 0.001) than the gastric body. As with lipase activity, there were no statistically significant differences in pepsin activity among age groups. Lipase and pepsin activity was also quantified in pinch biopsy specimens from the duodenum and duodenal bulb in 13 subjects. Contrary to lipase activity, which was almost completely absent from the duodenum or duodenal bulb, these sites contained low pepsin activity (9-78 pepsin units/mg protein). The data show that in infants and children, as previously reported in adults, gastric lipase is localized primarily in the gastric body. Tissue pepsin levels and localization, reported here for the first time, are similar to those of lipase, although, contrary to lipase, the gastric antrum has considerable pepsin activity. The identical levels of lipase and pepsin activities in infants, children, and adults indicate that the gastric phase of nutrient digestion is well developed at birth.
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PMID:Lipase and pepsin activity in the gastric mucosa of infants, children, and adults. 204

Serologically distinct group A streptococcal M proteins, the antiphagocytic determinants of the bacteria, have a highly repetitive sequence and exhibit a heptad periodicity characteristic of alpha-helical coiled-coil proteins. Based on the differences in the pattern of hepatad periodicity, the coiled-coil region of the complete M molecule has been divided into three distinct domains: I, II, and III. Domains I and II together constitute the variable part of M protein, whereas domain III is conserved among serotypes. Pepsin treatment of the M5, M6, and M24 streptococci results in a preferential cleavage of their M molecules between the predicted domains II and III, releasing biologically active fragments of the respective M proteins. Thus, a pepsin cleavage site at the junction of their variable and conserved regions is conserved in the M5, M6, and M24 proteins. In contrast, in the case of the M49 streptococci, the primary site of pepsin cleavage was observed to be within the conserved region of the M49 molecule, rather than at the junction of its variable and conserved regions. Despite containing part of the conserved region, the PepM49 protein is significantly smaller than the pepsin fragments of the M5, M6, and M24 proteins, which contain only the variable regions. However, in addition to the major PepM49 species, the pepsin digest of the type-49 streptococci also contained a smaller fragment, PepM49/a, as a minor component. Its formation was extremely sensitive to the pH of pepsin digestion. PepM49/a, which retains both the propensity to attain an alpha-helical conformation and the opsonic antibody epitope of the M49 molecule, contains only domains I and II like the other PepM proteins. Thus, as in the M5, M6, and M24 proteins, a pepsin cleavage site at the junction of the variable and conserved regions is indeed present in the M49 molecule, but is much less accessible relative to the other serotypes. Thus, the pepsin cleavage sites in the M protein correlate quite well with the boundaries of structurally distinct domains reflected by the predictive analysis. These sites apparently represent the flexible/hinge regions of the molecule. PepM49/a is the least repetitive and the shortest of the M protein pepsin fragments isolated so far. These results suggest that the flexibility of the interdomain regions in M protein may be dependent on the molecular size of their variable domains.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Domain structure and molecular flexibility of streptococcal M protein in situ probed by limited proteolysis. 208 76

The separation of pepsin isoenzymes 1, 2, 3 and 5 (gastricsin) in human gastric juice was effected by chromatography on Mono Q ion-exchanger, and slow-moving proteinase was purified to homogeneity by using a modified procedure incorporating a novel affinity-chromatography step. The pH-activity profiles of these enzymes with mucus glycoprotein and basement-membrane substrates were determined; the profiles for pepsin 2 were noticeably different, and, in general, the pH optima for the hydrolysis of basement membrane were more acidic. Pepsin 1 expressed larger specificity constants (kcat./Km) than pepsin 3 with a series of synthetic peptide substrates, reflecting greater binding (smaller Km) by pepsin 1. Inhibitor studies at pH 1.7 and 4.5 with a series of P2-substituted lactoyl-pepstatins implied that valine at position P2 was optimal for inhibiting pepsins 1, 2 and 3 but detrimental for pepsin 5, whereas lysine at position P2 was tolerated well by pepsin 5 but not by pepsins 1, 2 and 3. The potency of lactoyl-pepstatin with lysine at position P2 did not increase as a function of pH. P2-substituted lactoyl-pepstatins failed to show any inhibitory selectivity among pepsins 1, 2 and 3.
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PMID:Substrate and inhibitor studies with human gastric aspartic proteinases. 211 Nov 33

The digital flexor tendons of the neonate and adult horse have been compared with respect to variation in extracellular matrix composition along their length. Two pepsin-sensitive, acetic acid soluble proteins, molecular weight (Mr) 52 kD (np 52) and Mr 54 kD (np 54), were prominent throughout the length of neonatal tendons. In adult tendon, np 52 and np 54 were less abundant and restricted to the cannon (metacarpal) region. In contrast, a single pepsin- and collagenase-resistant protein of Mr 55 kD (fp 55) was exclusive to the fetlock (metacarpophalangeal joint) region regardless of age, although more distinct in the adult. Pepsin extracted fp 55 precipitated at 2.0 M sodium chloride: 0.5 M acetic acid and was further purified to homogeneity by bacterial collagenase digestion. Analysis of fp 55 amino acid composition revealed the presence of a large proportion of glycine residues (379 of 1001), suggesting a possible homology with the collagen family. These data demonstrate that the composition of equine digital flexor tendons varies with age, is heterogeneous along its length, and suggests that variation in tendon extracellular matrix composition is influenced by functional requirements.
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PMID:Age- and position-related heterogeneity of equine tendon extracellular matrix composition. 211 5

1. Three pepsins were purified from the gastric mucosa of Atlantic cod (Gadus morhua). 2. The enzymes, called Pepsin I and Pepsin IIa and b, had isoelectric points 6.9, 4.0 and 4.1, respectively, and digested hemoglobin at a maximal rate at a pH of approximately 3. 3. They resembled bovine cathepsin D in being unable to digest the mammalian pepsin substrate N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine. 4. Specificity constants (kcat/Km) for the cod pepsins were lower than for porcine pepsin, and they expressed higher substrate affinity and physiological efficiency at pH 3.5 than at pH 2. 5. The cod pepsins are glycoproteins, and their amino acid composition resembles that of porcine cathepsin D more than that of porcine pepsin. 6. The N-terminal sequence of Atlantic cod pepsins is substantially different from that of porcine pepsin. This indicates a significant evolutionary gap between fish and mammalian pepsins.
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PMID:Catalytic properties and chemical composition of pepsins from Atlantic cod (Gadus morhua). 211 46

Microdissection of acellular rat renal cortex with pepsin was carried out to investigate the morphological substructure of glomerular basement membrane (GBM) by high resolution SEM. Renal cortical blocks (less than 5 mm3) from adult male Sprague Dawley rats were rendered acellular by sequential detergent extraction and digested up to 184 hrs with 5 mg/ml pepsin (185 U/mg) in 0.5 M acetic acid (pH 2) at 10-15 degrees C. Samples were conventionally prepared for SEM, and observed at original magnifications of 500-100,000 diameters. At low magnifications (500-5,000x), acellular GBM surfaces appeared smooth at all digestion times. At higher magnifications (50,000-100,000x), control GBM surfaces were finely granular. Granule diameter ranged from 20-80 nm, with most between 30-40 nm. Pepsin digestion did not affect average granule size. Beginning at 44 hrs of digestion, intrinsic fibrillar structures comprised of linear arrays of 20-40 nm granules were observed on/in GBM surfaces. At later incubation times, this component of GBM became more extensive. At 160 hrs, the fibrillar arrays frequently bifurcated and showed distinctive "forked" termini, some of which comprised two sides of a triangle (120-150 nm on a side). Fork "handles" (310-350 nm in length) radiated from each angle of the triangle. These sometimes terminated in large granules (approximately 100 nm in diameter), two of which appeared to connect fibrillar arrays end-to-end. Together with other arrays, the interconnected triangles appeared to comprise a three-dimensional meshwork extending into the GBM and possibly providing support for, its granular components.
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PMID:High resolution SEM analysis of acellular glomerular basement membrane following pepsin digestion: intrinsic fibrillar structures. 213 83

A revised three-dimensional crystal structure of ethanol-inhibited porcine pepsin refined to an R-factor of 0.171 at 2.3 A resolution is presented and compared to the refined structures of the fungal aspartic proteinases: penicillopepsin, rhizopuspepsin, and endothiapepsin. Pepsin is composed of two nearly equal N and C domains related by an intra dyad. The overall polypeptide fold and active site structures are homologous for pepsin and the fungal enzymes. The weak inhibition of pepsin by ethanol can be explained by the presence of one or more ethanol molecules, in the vicinity of the active site carboxylates, which slightly alter the hydrogen-bonding network and which may compete with substrate binding in the active site. Structural superposition analysis showed that the N domains aligned better than the C-domains for pepsin and the fungal aspartic proteinases: 107-140 C alpha pairs aligned to 0.72-0.85 A rms for the N domains; 64-95 C alpha pairs aligned to 0.78-1.03 A rms for the C domains. The major structural difference between pepsin and the fungal enzymes concerns a newly described subdomain whose conformation varies markedly among these enzyme structures. The subdomain in pepsin comprises nearly 100 residues and is composed of two contiguous segments within the C domain (residues 192-212 and 223-299). the subdomain is connected, or "hinged," to a mixed beta-sheet that forms one of the structurally invariant, active site psi-loops. Relative subdomain displacements as large as a 21.0 degrees rotation and a 5.9 A translation were observed among the different enzymes. There is some suggestion in pepsin that the subdomain may be flexible and perhaps plays a structural role in mediating substrate binding, determining the substrate specificity, or in the activation of the zymogen.
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PMID:Revised 2.3 A structure of porcine pepsin: evidence for a flexible subdomain. 221 65

Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.
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PMID:Pepsinogen release and acid secretion from human and guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness. 221 92

The effect of secretin on acid and pepsin secretion and gastrin release in the totally isolated vascularly perfused rat stomach was studied. With the phosphodiesterase inhibitor isobutyl methylxanthine (IMX) added to the vascular perfusate, baseline acid secretion was 4.7 +/- 1.1 (mean +/- S.E.M.) mumol/h and baseline pepsin output 1147 +/- 223 micrograms/h. Secretin significantly inhibited acid output to a minimum of 1.4 +/- 0.2 mumol/h at a concentration of 25 pM in the vascular perfusate (P less than 0.01). Pepsin output was not significantly different from baseline at any of the secretin doses tested. Threshold secretin concentration for acid inhibition was 5 pM. IMX stimulated gastrin output from 48 +/- 9 pM in the basal state to 95 +/- 13 pM after IMX (P less than 0.01). Secretin inhibited gastrin release only at the maximal dose of 625 pM, when gastrin concentration in the venous effluent decreased from 93 +/- 19 to 68 +/- 19 pM after secretin. Thus, in the totally isolated vascularly perfused rat stomach secretin in physiological concentrations inhibits acid secretion by a direct action on the acid secretory process and not via gastrin inhibition. The study also suggests that gastrin release at least in part is mediated via increased intracellular cAMP.
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PMID:The effect of secretin on acid and pepsin secretion and gastrin release in the totally isolated vascularly perfused rat stomach. 243 26

The effect of the H2 agonist impromidine, gastrin 1-17 (G1-17), pentagastrin, and the M1 agonist McN-A-343 on pepsin secretion in the acid-inhibited totally isolated, vascularly perfused rat stomach was studied. Omeprazole produced a 97-98% inhibition of stimulated acid outputs. Base-line pepsin output after omeprazole was 712 +/- 278 micrograms/h (mean +/- SEM) and, after stimulation with impromidine, 1528 +/- 164 micrograms/h; G1-17, 1520 +/- 180 micrograms/h; and pentagastrin, 2063 +/- 605 micrograms/h. Output after McN-A-343 was 534 +/- 69 micrograms/h. Pepsin secretion after impromidine, G1-17, and pentagastrin was significantly (p less than 0.01) higher than base-line output. McN-A-343 had no significant effect on pepsin output in this model. Pepsin secretion after impromidine, G1-17, and pentagastrin was considerably lower than found in the same model with uninhibited acid output. This could be caused by decreased tubular 'washout' after acid inhibition, and, accordingly, no conclusions can be drawn as to the possible stimulatory effect of acid on pepsin secretion. However, the present study indicates that pepsin secretion can be stimulated directly by impromidine and (penta)gastrin without concomitant acidification of the gastric glands.
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PMID:Stimulated pepsin secretion after omeprazole-induced acid suppression in the totally isolated, vascularly perfused rat stomach. 243 47


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