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Medicinal Research Reviews Mar 2001Adenosine deaminase (ADA) is an enzyme of the purine metabolism which catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine,... (Review)
Review
Adenosine deaminase (ADA) is an enzyme of the purine metabolism which catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. This ubiquitous enzyme has been found in a wide variety of microorganisms, plants, and invertebrates. In addition, it is present in all mammalian cells that play a central role in the differentiation and maturation of the lymphoid system. However, despite a number of studies performed to date, the physiological role played by ADA in the different tissues is not clear. Inherited ADA deficiency causes severe combined immunodeficiency disease (ADA-SCID), in which both B-cell and T-cell development is impaired. ADA-SCID has been the first disorder to be treated by gene therapy, using polyethylene glycol-modified bovine ADA (PEG-ADA). Conversely, there are several diseases in which the level of ADA is above normal. A number of ADA inhibitors have been designed and synthesized, classified as ground-state and transition-state inhibitors. They may be used to mimic the genetic deficiency of the enzyme, in lymphoproliferative disorders or immunosuppressive therapy (i.e., in graft rejection), to potentiate the effect of antileukemic or antiviral nucleosides, and, together with adenosine kinase, to reduce breakdown of adenosine in inflammation, hypertension, and ischemic injury.
Topics: Adenosine Deaminase; Adenosine Deaminase Inhibitors; Animals; Enzyme Inhibitors; Genetic Therapy; Humans; Isoenzymes; Molecular Structure; Severe Combined Immunodeficiency; T-Lymphocytes
PubMed: 11223861
DOI: 10.1002/1098-1128(200103)21:2<105::aid-med1002>3.0.co;2-u -
Rheumatic Diseases Clinics of North... Nov 2023Deficiency of adenosine deaminase 2 (DADA2) is a monogenic vasculitis syndrome caused by biallelic mutations in the adenosine deaminase 2 gene. The diagnosis of DADA2 is... (Review)
Review
Deficiency of adenosine deaminase 2 (DADA2) is a monogenic vasculitis syndrome caused by biallelic mutations in the adenosine deaminase 2 gene. The diagnosis of DADA2 is confirmed by decreased enzymatic activity of ADA2 and genetic testing. Symptoms range from cutaneous vasculitis and polyarteritis nodosa-like lesions to stroke. The vasculopathy of DADA2 can affect many organ systems, including the gastrointestinal and renal systems. Hematologic manifestations occur early with hypogammaglobulinemia, lymphopenia, pure red cell aplasia, or pancytopenia. Treatment can be challenging. Tumor necrosis factor inhibitors are helpful to control inflammatory symptoms. Hematopoietic stem cell transplant may be needed to treat refractory cytopenias, vasculopathy, or immunodeficiency.
Topics: Humans; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Polyarteritis Nodosa; Vasculitis; Mutation
PubMed: 37821195
DOI: 10.1016/j.rdc.2023.06.004 -
Autoimmunity Reviews Jan 2021Autoimmune diseases patients are characterized by the autoimmune disorders, whose immune system can't distinguish between auto- and foreign- antigens. Thus, Immune... (Review)
Review
Autoimmune diseases patients are characterized by the autoimmune disorders, whose immune system can't distinguish between auto- and foreign- antigens. Thus, Immune homeostasis disorder is the key factor for autoimmune diseases development. Adenosine deaminase (ADA) is the degrading enzyme for an immunosuppressive signal - adenosine, and play an important role in immune homeostasis regulation. Increasing evidences have shown that ADA is involved in various autoimmune diseases. ADA activity were changed in multiple autoimmune diseases patients and could be served as a biomarker for clinical diagnosis. In this study, we analyze the change of ADA activity in patients with autoimmune diseases, and we underline its potential diagnostic value for autoimmune diseases patients.
Topics: Adenosine Deaminase; Autoimmune Diseases; Biomarkers; Humans
PubMed: 33197575
DOI: 10.1016/j.autrev.2020.102709 -
Journal of Clinical Immunology Oct 2017Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme of purine metabolism encoded by the Ada gene, is a cause of human severe combined immune... (Review)
Review
Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme of purine metabolism encoded by the Ada gene, is a cause of human severe combined immune deficiency (SCID). Numerous deleterious mutations occurring in the ADA gene have been found in patients with profound lymphopenia (T B NK), thus underscoring the importance of functional purine metabolism for the development of the immune defense. While untreated ADA SCID is a fatal disorder, there are multiple life-saving therapeutic modalities to restore ADA activity and reconstitute protective immunity, including enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) with autologous gene-corrected hematopoietic stem cells (HSC). We review the pathogenic mechanisms and clinical manifestations of ADA SCID.
Topics: Adenosine Deaminase; Animals; Disease Models, Animal; Humans; Severe Combined Immunodeficiency
PubMed: 28842866
DOI: 10.1007/s10875-017-0433-3 -
Medicinal Research Reviews Jan 2015Interest in adenosine deaminase (ADA) in the context of medicine has mainly focused on its enzymatic activity. This is justified by the importance of the reaction... (Review)
Review
Interest in adenosine deaminase (ADA) in the context of medicine has mainly focused on its enzymatic activity. This is justified by the importance of the reaction catalyzed by ADA not only for the intracellular purine metabolism, but also for the extracellular purine metabolism as well, because of its capacity as a regulator of the concentration of extracellular adenosine that is able to activate adenosine receptors (ARs). In recent years, other important roles have been described for ADA. One of these, with special relevance in immunology, is the capacity of ADA to act as a costimulator, promoting T-cell proliferation and differentiation mainly by interacting with the differentiation cluster CD26. Another role is the ability of ADA to act as an allosteric modulator of ARs. These receptors have very general physiological implications, particularly in the neurological system where they play an important role. Thus, ADA, being a single chain protein, performs more than one function, consistent with the definition of a moonlighting protein. Although ADA has never been associated with moonlighting proteins, here we consider ADA as an example of this family of multifunctional proteins. In this review, we discuss the different roles of ADA and their pathological implications. We propose a mechanism by which some of their moonlighting functions can be coordinated. We also suggest that drugs modulating ADA properties may act as modulators of the moonlighting functions of ADA, giving them additional potential medical interest.
Topics: Adenosine Deaminase; Animals; Drug Design; Humans
PubMed: 24933472
DOI: 10.1002/med.21324 -
The Journal of Allergy and Clinical... Jun 2020
Topics: Adenosine Deaminase; Genotype; Humans; Intercellular Signaling Peptides and Proteins; Metabolism, Inborn Errors; Phenotype
PubMed: 32353490
DOI: 10.1016/j.jaci.2020.04.023 -
Nihon Rinsho. Japanese Journal of... Jan 2003
Review
Topics: Adenosine Deaminase; Animals; Binding Sites; Deoxyadenosines; Humans; Mutation; Polymorphism, Genetic; Severe Combined Immunodeficiency; Substrate Specificity; Zinc
PubMed: 12629697
DOI: No ID Found -
Isozymes 1980
Review
Topics: Adenosine Deaminase; Amino Acids; Animals; Carbohydrates; Carrier Proteins; Chromosome Mapping; Dipeptidyl Peptidase 4; Humans; Isoelectric Focusing; Isoenzymes; Kinetics; Macromolecular Substances; Molecular Weight; Nucleoside Deaminases; Polymorphism, Genetic; Species Specificity
PubMed: 6115830
DOI: No ID Found -
Acta Medica Portuguesa 1991Adenosine deaminase is an enzyme that actively participates in the metabolism of the adenine nucleotides. It catalyzes the irreversible hydrolytic deamination of... (Review)
Review
Adenosine deaminase is an enzyme that actively participates in the metabolism of the adenine nucleotides. It catalyzes the irreversible hydrolytic deamination of deoxyadenosine and adenosine with the production of deoxyinosine and inosine respectively and of ammonia. This enzyme thus plays an important role in lympho-monocyte maturation and activation. The increase in its activity in different biological fluids (pleural, pericardial, peritoneal, intra-articular and cerebrospinal fluids) has been used as a rapid diagnostic test in tuberculosis infection. In human immunodeficiency virus infection, it was verified that enzymatic activity progressively increases in serum and blood cells, accompanying the natural evolution of the disease. The physiopathological mechanism has not been definitely established but the CD4+ lymphocytes and macrophages are pointed to as being accountable for the enzyme's increase in activity. For this reason, adenosine deaminase could be a marker of the cellular immune response. The study of adenosine deaminase activity in blood cells elucidated the diagnosis of severe combined immunodeficiency (due to a congenital lack of the enzyme) in 30 to 50% of the cases. One type of congenital hemolytic anemia is due to an exaggerated enzymatic activity in red blood cells.
Topics: Adenosine Deaminase; Clinical Enzyme Tests
PubMed: 1807098
DOI: No ID Found -
Clinical Immunology and Immunopathology Sep 1995
Review
Topics: Adenosine Deaminase; Genotype; Humans; Immunologic Deficiency Syndromes; Mosaicism; Mutation; Phenotype
PubMed: 7554472
DOI: 10.1016/s0090-1229(95)90288-0