Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.1 (chymotrypsin)
 10,938 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

TRH and pseudo-hormone (pyro Glu-His-amphetamine) were submitted to the digestion of chymotrypsin and prolidase and independently to the digestion of enzymes of the digestive track: pepsin (stomach), pancreatins (pancreas) and enzymes extracted from the intestinal mucosa (small intestine). Using thin layer chromatography and high voltage electrophoresis techniques to detect enzymic digestion products, only intact TRH and pseudo-hormone were found, indicating that both entities were, under the conditions used, resistant to in vitro digestion by enzymes of the digestive tract.
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PMID:Evidence for the resistance of thyrotropin-releasing hormone (TRH) and pseudo-hormone, pyroglutamyl histidyl-amphetamine, to degradation by enzymes of the digestive tract in vitro. 11 43

Purified bovine beta-casein was digested in vitro with varying mixtures of purified proteinases and peptidases including trypsin, chymotrypsin, dipeptidyl peptidase IV (DP IV), aminopeptidase M and prolidase. In digestion mixtures without DP IV the yield of free amino acids was considerably lower than in the corresponding assays with this peptidase. Especially, the release of proline increases drastically from almost zero to the theoretical amount in the presence of DP IV. Quantitative results indicated that the specificities of the two microvillar peptidases (aminopeptidase M and DP IV) optimally complemented each other. This effect elucidates the hitherto obscure physiological role of intestinal DP IV. A similar effect may also apply to other caseins and nutritional proteins.
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PMID:Complementary action of dipeptidyl peptidase IV and aminopeptidase M in the digestion of beta-casein. 287 57

An inhibitor of sodium-potassium-ATPase has been partially purified from the culture medium obtained from hypothalamic cells maintained in a capillary membrane perfusion system, and some of the properties of this inhibitory factor have been investigated. Gel filtration (Sephadex G-25 Superfine) of heat-treated medium (80 degrees C for 10 min) resulted in elution of inhibitory activity in the post-salt fraction. These fractions inhibited active (i.e. sodium-potassium-ATPase-mediated) sodium transport in intact human erythrocytes, displaced [3H]ouabain from its binding site, and directly inhibited canine kidney sodium-potassium-ATPase as measured by NADH oxidation. High-performance liquid chromatography (on Hypersil ODS) of these fractions after desalting yielded one region which showed inhibitory activity on all three assays. Inhibition of sodium-potassium-ATPase was dose-related and filtered through an Amicon UM10 membrane. Incubation of this material with dispase, carboxypeptidase A, chymotrypsin, and prolidase destroyed inhibitory activity, whereas trypsin and leucine aminopeptidase were ineffective. These studies show that hypothalamic neurones release a low molecular weight heat-stable peptide which inhibits active sodium transport, ouabain binding, and sodium-potassium-ATPase.
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PMID:Characterization and partial purification of the sodium-potassium-ATPase inhibitor released from cultured rat hypothalamic cells. 299 73

1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c., and its effects on de-endothelialized rabbit aortic strips were investigated. 2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips. 3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l. 4. Both ASTI and ouabain caused a significantly greater (P less than 0.01) calcium retention than control medium in aortic strips. 5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective. 6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.
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PMID:Calcium retention and increased vascular reactivity caused by a hypothalamic sodium transport inhibitor. 340 35

In an effort to further develop the technique of isomer-specific proteolysis, a number of proline-containing substrates were subjected to hydrolysis in the presence of chymotrypsin, trypsin, or prolidase. The objective was to determine whether direct hydrolysis of the cis form of the substrate could occur and, if so, the extent to which it is slower than the hydrolysis of the equivalent trans form. It is shown that for both peptide and amide substrates, which contain proline at the P2 position, the cis form can be hydrolyzed directly by either chymotrypsin or trypsin, in contrast to earlier suggestions in the literature. For similar amide substrates, it was found that chymotrypsin has a lower catalytic efficiency for the cis form, relative to the trans form, by a factor of 20 000 while, for trypsin and its substrate, the cis form was cleaved about 2000 times less efficiently. Results for a trypsin substrate with proline at the P2' position, rather than the P2 position, were quite different however, since there was no indication that the cis form could be directly cleaved even at the highest enzyme concentration. There was also no indication that prolidase could cleave the dipeptide Phe-Pro when the active bond itself is in the cis form. These collective results suggest that the ability of proteases to cleave a substrate with a cis peptide bond depends strongly on the location of the cis bond relative to the active bond that is being cleaved.
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PMID:Isomer-specific proteolysis of model substrates: influence that the location of the proline residue exerts on cis/trans specificity. 408 35

An inhibitor(s) for post-proline cleaving enzyme was checked by using a fluorogenic substrate, Z-Gly-Pro-4-methyl coumarinamide, and was found to be distributed widely in rat and porcine organs. The highest inhibitory activity on the enzyme was observed in pancreas and the inhibitor was partially purified from porcine pancreas extract by heat treatment, chromatographies on DEAE-Sephadex and Sephadex G-50 and affinity chromatography on trypsin-Sepharose. This inhibitor was very stable against temperature, pH and trichloroacetic acid treatment. The molecular weight was estimated to be 6500 by gel filtration. This inhibitor was highly specific for prolyl endopeptidases from mammals and Flavobacterium and inhibited the enzyme competitively. It acted neither on proline specific exopeptidases such as dipeptidyl aminopeptidase IV, proline aminopeptidase, prolidase, nor usual endopeptidases such as trypsin and alpha-chymotrypsin.
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PMID:An inhibitor for post-proline cleaving enzyme; distribution and partial purification from porcine pancreas. 618 66

Many biologically important peptide sequences contain proline. It confers unique conformational constraints on the peptide chain in that the side-chain is cyclized back onto the backbone amide position. Inside an alpha-helix the possibility of making hydrogen bonds to the preceding turn is lost and a kink will be introduced. The conformational restrictions imposed by proline motifs in a peptide chain appear to imply important structural or biological functions as can be deduced from their often remarkably high degree of conservation as found in many proteins and peptides, especially cytokines, growth factors, G-protein-coupled receptors, V3 loops of the HIV envelope glycoprotein gp 120, and neuro- and vasoactive peptides. Only a limited number of peptidases are known to be able to hydrolyze proline adjacent bonds. Their activity is influenced by the isomeric state (cis-trans) as well as the position of proline in the peptide chain. The three proline specific metallo-peptidases (aminopeptidase P, carboxypeptidase P and prolidase) are activated by Mn2+, whereas the three serine type peptidases cleaving a post proline bond (prolyl oligopeptidase, dipeptidyl peptidase IV, and prolylcarboxypeptidase) share the sequential order of the catalytic Ser-Asp-His triade, which differentiates them from the chymotrypsin (His-Asp-Ser) and subtilisin (Asp-His-Ser) families. An endo or C terminal Pro-Pro bond and an endo pre-Pro peptide bond possess a high degree of resistance to any mammalian proteolytic enzyme.
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PMID:Proline motifs in peptides and their biological processing. 760 38