Adenosine deaminase: Functional implications and different classes of inhibitors

Adenosine deaminase (ADA) is an enzyme of the purine metabolism which catal yzes the irreversible deamination of adenosine and deoxyadenosine to inosin e and deoxyinosine, respectively, This ubiquitous enzyme has been found in a wide variety of microorganisms, plants. and invertebrates. In addition, i t is present in all mammalian cells that play a central role in the differe ntiation and maturation of the lymphoid system, However, despite a number o f studies performed to date, the physiological role played by ADA in the di fferent tissues is not clear. Inherited ADA deficiency causes severe combin ed immunodeficiency desease (ADA-SCID), in which both B-cell and T-cell dev elopment is impaired. ADA-SCID has been the first disorder to be treated by gene therapy, using polyethene glycol-modified bovine ADA (PEG-ADA). Conve rsely, 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 eff ect of antileukemic or antiviral nucleosides, and, together with adenosine kinase, to reduce breakdown of adenosine in inflammation, hypertension, and ischemic injury. (C) 2001 John Wiley & Sons, Inc.