Kinetic investigation of the hydrolysis of aminoacyl p-nitroanilides by dipeptidyl peptidase IV from human and pig kidney

Heins, Jochen; Neubert, Klaus; Barth, A.; Canizaro, Peter C.; Běhal, Francis J.

doi:10.1016/0167-4838(84)90230-9

Cited by 20 publications

(7 citation statements)

References 14 publications

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“…In a strain of rats lacking DPP IV, this metabolite is not formed [14]. DPP IV is highly specific and has strict substrate requirements [18,19], raising the possibility of developing analogues which the enzyme is unable to cleave. Studies with another peptide substrate of DPP IV, growth hormone-releasing factor (GRF), have shown that analogues with N-terminal amino acid substitutions have some resistance to the enzyme's action [20].…”

Section: ó Springer-verlag 1998mentioning

confidence: 99%

Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity

et al. 1998

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Section: ó Springer-verlag 1998mentioning

confidence: 99%

Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity

et al. 1998

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“…In circulation both, BK and Lys-BK and their des-Arg forms are short-lived being immediately degraded into inactive products by aminopeptidase P (AAP), neutral endopeptidase (NEP), dipeptidyl peptidase IV (DPPIV) and angiotensin-converting enzyme (ACE), respectively ( Figure 1) (12,(35)(36)(37)(38)(39)(40). The short half-life also explains why the measurement of BK in plasma is troublesome and critically depends on preanalytical handling of patient plasma samples (13).…”

Section: Clinical Picturementioning

confidence: 99%

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

Zeerleder

Levi

2016

Annals of Medicine

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Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitordependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation. ä KEY MESSAGESInadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema. Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis. Submucosal edema formation in hereditary and acquired C1-inhibitor-dependent angioedema is potentially life threatening and can occur at any age. To date effective therapies for acute and prophylactic treatment are available. ARTICLE HISTORY

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“…This study on human lung aminopeptidase P is a part of our overall study on the contributions of various kinin catabolizing enzymes to the total rate of kinin catabolism in lung; the other enzymes include (a) postproline endopeptidase (cleaving enzyme) which we have detected in human lung and which has been shown by Koida and Walter (20) to cleave bradykinin, (b) dipeptidyl-peptidase IV (which will cleave the dipeptide, Pro-Pro, from des-[Arg'l-bradykinin, the product of aminopeptidase P action) which we have recently purified from human kidney and human lung (21,22), (c) two endopeptidases, and of course (d) carboxypeptidase N and Kinase 11. Our results provide enzymologic evidence for a kinin cleaving enzyme, other than carboxypeptidase N and Kinase 11, in human lung.…”

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confidence: 97%

Cleavage of the ARG-PRO Bond of Bradykinin by a Human Lung Peptidase: Isolation, Characterization, and Inhibition by Several -Lactam Antibiotics

Sidorowicz

Szechiński

Canizaro

et al. 1984

Experimental Biology and Medicine

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An aminopeptidase P (EC 3.4.1 1.9) that cleaves the Arg1-Pro2 bond of bradykinin has been isolated for the first time from human lung and purified 473-fold. The enzyme also catalyzes the cleavage of argnine from des-[Arg'l-bradykinin and the hydrolysis of several X-proline dipeptides including L-arginyl-L-proline, L-leucyl-L-proline, and L-alanyl-L-proline. Purified enzyme was routinely assayed (after initial identification with des-[Arg'l-bradykinin) with L-leucyl-L-proline. The molecular weight, in nondenaturing buffers, is 188,000 k 8500 Da. The pH optimum was 8.0 with argnyl-proline, and was 6.8 with leucyl-proline. Chelating agents do not inactivate the enzyme, but rather only remove loosely bound cations that stimulate the enzyme. Manganese is the principal cation that stimulates the enzyme. The enzyme is inhibited by several P-lactam antibiotics, cephalexin and oxacillin being the most effective of those tested. The antibiotic inhibition is time and temperature dependent, and it is not fully reversible by exhaustive dialysis of the antibiotic-treated enzyme.

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Kinetic investigation of the hydrolysis of aminoacyl p-nitroanilides by dipeptidyl peptidase IV from human and pig kidney

Cited by 20 publications

References 14 publications

Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity

Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

Cleavage of the ARG-PRO Bond of Bradykinin by a Human Lung Peptidase: Isolation, Characterization, and Inhibition by Several -Lactam Antibiotics

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