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Adenosine deaminase: Functional implications and different classes of inhibitors
Author(s) -
Cristalli Gloria,
Costanzi Stefano,
Lambertucci Catia,
Lupidi Giulio,
Vittori Sauro,
Volpini Rosaria,
Camaioni Emidio
Publication year - 2001
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/1098-1128(200103)21:2<105::aid-med1002>3.0.co;2-u
Subject(s) - adenosine deaminase , adenosine deaminase deficiency , inosine , purine metabolism , purine nucleoside phosphorylase , adenosine kinase , adenosine deaminase inhibitor , adenosine , adar , severe combined immunodeficiency , amp deaminase , deoxycoformycin , enzyme , purine , biology , deoxyadenosine , biochemistry , chemistry , gene , rna editing , gene expression
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 desease (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 polyethene glycol‐modified bovine ADA (PEG‐ADA). Conversely, there are several diseases in which the level of ADA is above normal. A number of ADA inibitors 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. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 2, 105–128, 2001