Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The degradation of several bioactive peptides and proteins by purified human dipeptidyl peptidase IV is reported. It was hitherto unknown that human gastrin-releasing peptide, human chorionic gonadotropin, human pancreatic polypeptide, sheep prolactin, aprotinin, corticotropin-like intermediate lobe peptide and (Tyr-)melanostatin are substrates of this peptidase. Kinetic constants were determined for the degradation of a number of other natural peptides, including substance P, the degradation of which has been described earlier in a qualitative manner. Generally, small peptides are degraded much more rapidly than proteins. However, the Km-values seem to be independent of the peptide chain length. The influence of the action of dipeptidyl peptidase IV on the biological function of peptides and proteins is discussed.
 ...
PMID:The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV from human placenta. 198 12

The purification and kinetic characterization of cholinesterase from blood plasma (pseudocholinesterase; butyrylcholinesterase: EC 3.1.1.8) is described. The hydrolysis of the artificial peptide substrate Lys-Pro-p-nitroanilide served as a model of the second step in degradation of substance P by dipeptidyl peptidase IV. The substrate is hydrolyzed by a gel-electrophoretic homogeneous cholinesterase preparation with a reaction rate of 5.8 mumol/min X mg and a KM value of 0.12 mmol/l. The proteolytic reaction could not be affected with typical cholinesterase inhibitors NaF and dibucain. On the other hand Lys (pNO2-Z)-Pro and a specific suicide substrate (diacylhydroxylamine derivative) inhibit the activity in a manner analogous to dipeptidyl peptidase IV. Though these active site-directed inhibitors also influenced the benzoylcholine hydrolyzing activity of serum cholinesterase, we conclude from the data that dipeptidyl peptidase IV was the true Lys-Pro-p-nitroanilide cleaving activity. Furthermore, the conclusion can also be drawn that hydrolysis of substance P reported by Lockridge 1982 is caused by the contamination that cannot be completely separated from the esterase during the purification method used.
 ...
PMID:Contamination of highly purified human serum cholinesterase by dipeptidyl peptidase IV causing hydrolysis of substance P. 243 Mar 7

In terminally differentiated epidermal cells dipeptidyl peptidase IV (EC 3.4.14.5) (DPP IV) is present mainly in a soluble form. We purified the enzyme from 2-day-old rat cornified cells to homogeneity by Sephadex G-200 and Mono-Q column chromatography and finally HPLC gel filtration on G3000SW. The enzyme was estimated to be Mr 190,000 by HPLC gel filtration and Mr 90,000 by sodium dodecyl sulfate-electrophoresis. The enzyme showed general properties reported for detergent-solubilized DPP IV from other tissues. It was Con A binding and almost completely inhibited by 1 mM diisopropyl fluorophosphate and Diprotin A. The pI was 5.6 and the pH optimum was 7.5. The specific activity for Gly-Pro-p-nitroanilide was 31.9 units/mg. HPLC analysis demonstrated the release of dipeptides of the N-terminal of substance P, beta-casomorphin, and their related peptides. A stoichiometric reaction of the enzyme on substance P was observed. The epidermal DPP IV had a Km of 0.3 mM and a kcat of 50.3 s-1 for substance P and the Km value decreased by shortening the peptide from the carboxyl-terminal amino acids. The enzyme hydrolyzed human and bovine beta-casomorphin with Km values of 0.025 and 0.05 mM, respectively. Shortening the bovine beta-casomorphin peptide chain did not affect enzyme affinity.
 ...
PMID:Soluble dipeptidyl peptidase IV from terminal differentiated rat epidermal cells: purification and its activity on synthetic and natural peptides. 246 Nov 66

Human serum cleaves two dipeptides from the N-terminus of the neurohormone substance P. It has been suggested that this degrading activity is inherent to serum cholinesterase. We oppose this, because it turned out that highly purified serum cholinesterase contains traces of dipeptidyl peptidase IV, an enzyme known to attack the N-terminus of substance P. The peptidase is incompletely separated from cholinesterase during the procainamide-gel affinity chromatography as the last step of the usual purification procedure. Physostigmine completely inhibits the hydrolysis of butyrylthiocholine by such purified cholinesterase preparations, but not their substance P-degrading activity. Vice versa, epsilon-carbobenzoxy-lysylproline, an inhibitor of dipeptidyl peptidase IV, inhibits the peptidase activity of these preparations more than their esterase activity. After rechromatography on procainamide gel the peptidase is completely separated and the remaining cholinesterase has lost its substance P-degrading activity. We conclude that the N-terminal region of substance P is not degraded by cholinesterase but by the contaminating dipeptidyl peptidase IV, a different serine enzyme.
 ...
PMID:Substance P in human plasma is degraded by dipeptidyl peptidase IV, not by cholinesterase. 258 Sep 48

Dipeptidyl peptidase IV was enriched about 2000-fold from lymphocytes of chronic lymphocytic leukemia of T-type. The purification procedure involved immunoaffinity chromatography using antibodies raised with highly purified dipeptidyl peptidase IV from human placenta. The lymphocytic peptidase had a subunit Mr of 110,000. Its kinetic properties were similar to those of the placenta enzyme: Two N-terminal dipeptides were cleaved from substance P and from casomorphin, and naphthylamine was released from X-prolynaphthylamides with Km-values of about 0.02 mM. The lymphocytic peptidase was 10-fold less sensitive to zinc inhibition as compared to the placenta enzyme. Isoelectric focussing patterns of dipeptidyl peptidase IV in leukemic lymphocytes and in normal T-lymphocytes were very similar.
 ...
PMID:Characterization of dipeptidyl peptidase IV from lymphocytes of chronic lymphocytic leukemia of T-type. 287 12

Dipeptidyl peptidase IV is a very specific protease that attracts growing scientific interest during the last few years. The enzyme has been purified to homogeneity from various human tissues. Histochemically, this protease is found at certain border lines of many organ compartments, as in the proximal tubuli of kidney, in the bile canaliculi of liver, in the capillary endothel, or in the myofibroblasts of placenta. In the blood, especially T-helper lymphocytes contain this enzyme. Dipeptidyl peptidase IV seems to be predestinated for regulatory functions, because it is located on the outer membranes of these cells. The peptidase very specifically degrades substance P. Thus, it is discussed whether the system substance P/dipeptidyl peptidase IV is involved in the regulation of blood pressure, especially in the placenta. On the other hand, the specific attack of the peptidase on the alpha-chain of monomeric fibrin considerably reduces the clotting potency of these molecules. Therefore, dipeptidyl peptidase IV may also be involved in the regulation of blood coagulation in intact vessels, especially because the capillary endothel is lined with this enzyme. The plasma zinc concentration seems to influence the peptidase activity. An increase in plasma zinc stimulates various factors that promote blood clotting.
 ...
PMID:[Has dipeptidyl peptidase IV an effect on blood pressure and coagulation?]. 619 52

Proline-containing dipeptidyl-4-nitroanilides have been synthesised and subjected to dipeptidyl peptidase IV-catalysed hydrolysis at high enzyme concentrations to collect information on the conformational specificity of the enzyme active site for a nonscissile bond. Descriptions of the biphasic kinetics were carried out in terms of cis/trans interconversion of the substrates. The results show that the enzyme can cleave only the trans-conformation of the substrate. The competitive inhibition by Gly-Pro-OH and Ala-Pro-OH is also specific for the trans form of the dipeptides. The interpretation of the results obtained from these kinetic studies has led to proposals for the stepwise cleavage of biologically active peptides like substance P and beta-casomorphine by dipeptidyl peptidase IV.
 ...
PMID:The conformation around the peptide bond between the P1- and P2-positions is important for catalytic activity of some proline-specific proteases. 634 Jul 41

Dipeptidyl peptidase IV (dipeptidyl-peptide hydrolase, EC 3.4.14.5), an enzyme that participates in the catabolism of bradykinin and Substance P as well as the post-translational processing of various other peptides, has been purified from human and pig kidney. The assay reaction involved the cleavage of p-nitroaniline (pNA) from various dipeptidyl p-nitroanilides. The specific activities of the human and pig enzyme (with Gly-Pro-pNA at pH 7.6) were 49.2 and 45.8, respectively. The dependence of initial reaction velocity on substrate concentration was determined for a variety of dipeptidyl p-nitroanilides over the concentration range 0.05 to 2.0 mM. Most of the substrates tested produced significant non-hyperbolic behavior for the function v vs. S at concentrations above 0.5 mM. As to differences between the two enzymes, the pig enzyme exhibited featureless (i.e., hyperbolic) behavior with Glu-Pro-pNA concentrations as high as 2.0 mM, whereas the human enzyme produced significant non-hyperbolic behavior for the function v vs. S, beginning at S = 0.4 mM. Thus, the human and pig dipeptidyl peptidases IV are kinetically distinct enzyme forms.
 ...
PMID:Kinetic investigation of the hydrolysis of aminoacyl p-nitroanilides by dipeptidyl peptidase IV from human and pig kidney. 636 69

In the human placenta, besides the fetal blood vessel system a second extravascular contractile system exists. It is localized in the chorionic plate and runs in a longitudinal direction and adjacent to fetal blood vessels into the stem villi, where it forms perivascular contractile sheaths. Characteristically, cells of the extravascular contractile system are extremely long and spindle-shaped and give rise to fine cell processes, by which they obviously contact each other or insert into the basement membrane of the trophoblast. They show immunoreactivity with desmin, vimentin, alpha-actin, myosin, nitric oxide synthase type I (brain form) and dipeptidyl peptidase IV. The ultrastructure suggests that cells of the extravascular contractile system are related to smooth muscle cells, including subpopulations with myofibroblastic features. In stem villi a few cells are nitric oxide synthase type I immunoreactive. These cells are thought to be specialized smooth-muscle-like cells of the extravascular contractile system or cells of the extravascular contractile system related to paraneurons that generate nitric oxide, which, in turn, may modulate the tone of perivascular contractile sheaths. The high dipeptidyl peptidase IV activity suggests that modulation of the extravascular contractile system may also occur by substance P.
 ...
PMID:The extravascular contractile system in the human placenta. Morphological and immunocytochemical investigations. 753 54

To elucidate the mechanisms of inactivation of the ecdysiostatic peptide trypsin-modulating oostatic factor (Neb-TMOF) in the blue blowfly Calliphora vicina, we investigated its proteolytic degradation. In homogenates and membrane and soluble fractions, this hexapeptide (sequence: NPTNLH) was hydrolyzed into two fragments, NP and TNLH, suggesting the involvement of a proline-specific dipeptidyl peptidase. The dipeptidyl peptidase activity was highest in the late larval stage. It was purified 240-fold from soluble fractions of pupae of mixed age and classified on the basis of several catalytic properties as an invertebrate homologue of mammalian dipeptidyl peptidase IV (EC 3.4.14.5). Fly dipeptidyl peptidase IV has a molecular mass of 200 kDa, showed a pH optimum of 7.5-8.0 with the chromogenic substrate Gly-Pro-4-nitroanilide, and cleaved other chromogenic substrates with penultimate Pro or, with lower activity, Ala. It liberated Xaa-Pro dipeptides from the N-terminus of several bioactive peptides including substance P, neuropeptide Y, and peptide YY but not from bradykinin, indicating that the peptide bond between the two proline residues was resistant to cleavage. Fly dipeptidyl peptidase belongs to the serine class of proteases as the mammalian enzyme does; the fly enzyme, however, is not inhibited by several selective or nonselective inhibitors of its mammalian counterpart. It is suggested that dipeptidyl peptidases exert a regulatory role for the clearance not only of TMOF in files but for other bioactive peptides in various invertebrates.
 ...
PMID:Proline-specific dipeptidyl peptidase from the blue blowfly Calliphora vicina hydrolyzes in vitro the ecdysiostatic peptide trypsin-modulating oostatic factor (Neb-TMOF). 943 95


1 2 3 4 Next >>