Influence of dipeptidyl peptidase IV on enzymatic properties of adenosine deaminase.

The importance of ADA (adenosine deaminase) in the immune system and the role of its interaction with an ADA-binding cell membrane protein dipeptidyl peptidase IV (DPPIV), identical to the activated immune cell antigen, CD26, has attracted the interest of researchers for many years. To investigate the specific properties in the structure-function relationship of the ADA/DPPIV-CD26 complex, its soluble form, identical to large ADA (LADA), was isolated from human blood serum, human pleural fluid and bovine kidney cortex. The kinetic constants (Km and Vmax) of LADA and of small ADA (SADA), purified from bovine lung and spleen, were compared using adenosine (Ado) and 2'-deoxyadenosine (2'-dAdo) as substrates. The Michaelis constant, Km, evidences a higher affinity of both substrates (in particular of more toxic 2'-dAdo) for LADA and proves the modulation of toxic nucleoside neutralization in the extracellular medium due to complex formation between ADA and DPPIV-CD26. The values of Vmax are significantly higher for SADA, but the efficiency, Vmax/Km, in LADA-catalyzed 2'-dAdo deamination is higher than that in Ado deamination. The interaction of all enzyme preparations with derivatives of adenosine and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was studied. 1-DeazaEHNA and 3-deazaEHNA demonstrate stronger inhibiting activity towards LADA, the DPPIV-CD26-bound form of ADA. The observed differences between the properties of the two ADA isoforms may be considered as a consequence of SADA binding with DPPIV-CD26. Both SADA and LADA indicated a similar pH-profile of adenosine deamination reaction with the optimum at pHs 6.5-7.5, while the pH-profile of dipeptidyl peptidase activity of the ADA/DPPIV-CD26 complex appeared in a more alkaline region.

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Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders

Clinical Science ◽

10.1042/cs20040302 ◽

2005 ◽

Vol 108 (4) ◽

pp. 277-292 ◽

Cited By ~ 204

Author(s):

Mark D. GORRELL

Keyword(s):

Gene Family ◽

Cell Biology ◽

Cancer Biology ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Soluble Form ◽

Peptidase Activity ◽

Tissue Remodelling ◽

Glucagon Like Peptide 1 ◽

Novel Target

DP (dipeptidyl peptidase) IV is the archetypal member of its six-member gene family. Four members of this family, DPIV, FAP (fibroblast activation protein), DP8 and DP9, have a rare substrate specificity, hydrolysis of a prolyl bond two residues from the N-terminus. The ubiquitous DPIV glycoprotein has proved interesting in the fields of immunology, endocrinology, haematology and endothelial cell and cancer biology and DPIV has become a novel target for Type II diabetes therapy. The crystal structure shows that the soluble form of DPIV comprises two domains, an α/β-hydrolase domain and an eight-blade β-propeller domain. The propeller domain contains the ADA (adenosine deaminase) binding site, a dimerization site, antibody epitopes and two openings for substrate access to the internal active site. FAP is structurally very similar to DPIV, but FAP protein expression is largely confined to diseased and damaged tissue, notably the tissue remodelling interface in chronically injured liver. DPIV has a variety of peptide substrates, the best studied being GLP-1 (glucagon-like peptide-1), NPY (neuropeptide Y) and CXCL12. The DPIV family has roles in bone marrow mobilization. The functional interactions of DPIV and FAP with extracellular matrix confer roles for these proteins in cancer biology. DP8 and DP9 are widely distributed and indirectly implicated in immune function. The DPL (DP-like) glycoproteins that lack peptidase activity, DPL1 and DPL2, are brain-expressed potassium channel modulators. Thus the six members of the DPIV gene family exhibit diverse biological roles.

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The CP-I Subunit of Adenosine Deaminase Complexing Protein from Calf Kidney Is Identical to Human, Mouse, and Rat Dipeptidyl Peptidase IV

Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology ◽

10.1016/s0305-0491(97)00327-1 ◽

1998 ◽

Vol 119 (2) ◽

pp. 289-292 ◽

Cited By ~ 12

Author(s):

Itzhak Ben-Shooshan ◽

Abraham H Parola

Keyword(s):

Adenosine Deaminase ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv

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N-linked glycosylation of dipeptidyl peptidase IV (CD26): Effects on enzyme activity, homodimer formation, and adenosine deaminase binding

Protein Science ◽

10.1110/ps.03352504 ◽

2004 ◽

Vol 13 (1) ◽

pp. 145-154 ◽

Cited By ~ 39

Author(s):

K. Aertgeerts

Keyword(s):

Enzyme Activity ◽

Adenosine Deaminase ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv

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Biosynthesis of intestinal microvillar proteins. Pulse-chase labelling studies on maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV

Biochemical Journal ◽

10.1042/bj2100389 ◽

1983 ◽

Vol 210 (2) ◽

pp. 389-393 ◽

Cited By ~ 23

Author(s):

E M Danielsen ◽

H Sjöström ◽

O Norén

Keyword(s):

Organ Culture ◽

Membrane Fraction ◽

Bound State ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Soluble Form ◽

Membrane Bound ◽

Aminopeptidase A ◽

High Mannose ◽

Small Intestinal

The biogenesis of three intestinal microvillar enzymes, maltase-glucoamylase (EC 3.2.1.20), aminopeptidase A (aspartate aminopeptidase, EC 3.4.11.7) and dipeptidyl peptidase IV (EC 3.4.14.5), was studied by pulse-chase labelling of pig small-intestinal explants kept in organ culture. The earliest detectable forms of the enzymes were polypeptides of Mr 225000, 140000 and 115000 respectively. These were found to represent the enzymes in a ‘high-mannose’ state of glycosylation, as judged by their susceptibility to treatment with endo-beta-N-acetylglucosaminidase H (EC 3.2.1.96). After about 40-60 min of chase, maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV were further modified to yield the mature polypeptides of Mr 245000, 170000 and 137000 respectively, which were expressed at the microvillar membrane after 60-90 min of chase. The fact that the enzymes before reaching the microvillar membrane were found in a Ca2+-precipitated membrane fraction (intracellular and basolateral membranes), but not in soluble form, indicates that during biogenesis maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV are transported and assembled in a membrane-bound state.

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Non-substrate peptides influencing dipeptidyl peptidase IV/CD26 activity and immune cell function

Frontiers in Bioscience ◽

10.2741/2920 ◽

2008 ◽

Vol Volume (13) ◽

pp. 3194 ◽

Cited By ~ 1

Author(s):

Sabine Wrenger

Keyword(s):

Cell Function ◽

Immune Cell ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Immune Cell Function

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Bestatin and bacitracin inhibit porcine kidney cortex dipeptidyl peptidase IV activity and reduce human melanoma MeWo cell viability

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2020.08.157 ◽

2020 ◽

Vol 164 ◽

pp. 2944-2952

Author(s):

Laura Rivera Méndez ◽

Yarini Arrebola ◽

Mario E. Valdés-Tresanco ◽

Lisset Díaz-Guevara ◽

Gretchen Bergado ◽

...

Keyword(s):

Cell Viability ◽

Dipeptidyl Peptidase ◽

Human Melanoma ◽

Dipeptidyl Peptidase Iv ◽

Kidney Cortex ◽

Porcine Kidney ◽

Mewo Cell

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Adenosine deaminase, dipeptidyl peptidase-IV activities and lipid peroxidation are increased in the saliva of obese young adult

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-1086 ◽

2015 ◽

Vol 53 (7) ◽

Cited By ~ 8

Author(s):

Eduardo Ottobelli Chielle ◽

Gabriela Bonfanti ◽

Karine Santos De Bona ◽

Rafael Noal Moresco ◽

Maria Beatriz Moretto

Keyword(s):

Lipid Peroxidation ◽

Adenosine Deaminase ◽

Inflammatory Diseases ◽

Dipeptidyl Peptidase ◽

Normal Weight ◽

Dipeptidyl Peptidase Iv ◽

Salivary Biomarkers ◽

The Metabolic Syndrome ◽

Dpp Iv ◽

Young Subjects

AbstractObesity is the hallmark of the metabolic syndrome representing a major global health problem. It is considered a state of chronic inflammation with minimal exploration of salivary biomarkers. Thus, the intent of the present study was to assess the activities of salivary dipeptidyl peptidase IV (DPP-IV), adenosine deaminase (ADA) and lipid peroxidation in obese young and overweight young subjects.ADA, DPP-IV activities and lipid peroxidation were investigated in saliva, as well as insulin, glucose, HbASalivary ADA and DPP-IV activities as well as lipid peroxidation were higher in patients with obesity compared to the normal weight group. Correlations between ADA/DPP-IV activities, lipid peroxidation/ADA activity, ADA activity/hip circumference and BMI/weight were observed.Our results indicate that the increase in the salivary ADA and DPP-IV activities as well as in the lipid peroxidation could be related of the regulation to various aspects of adipose tissue function and inflammatory obesity. It is suggested that these salivary biomarkers may be used as biochemical test in clinical abnormalities present in obesity, in the absence of oral inflammatory diseases.

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