Adenosine deaminase (ADA) (ADA)

Adenosine deaminase (ADA) is a critical enzyme in the purine salvage pathway that catalyzes the irreversible hydrolytic deamination of adenosine and 2-deoxyadenosine to inosine and 2-deoxyinosine, respectively [1]. While expressed ubiquitously, its activity is most vital in lymphoid tissues, where it is essential for the development, maintenance, and function of T, B, and NK lymphocytes [2]. A genetic deficiency in this enzyme leads to the systemic accumulation of toxic metabolites, particularly deoxyadenosine triphosphate (dATP), which inhibits DNA synthesis and induces apoptosis in lymphoid progenitors, resulting in Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) [3]. Therapeutic strategies focus on restoring enzymatic activity to detoxify the cellular environment, either through enzyme replacement therapy (ERT) using pegylated bovine or recombinant ADA, or through gene therapy [4]. Gene therapy involves the transduction of autologous hematopoietic stem cells with a functional ADA gene to provide a long-term, endogenous source of the enzyme, thereby facilitating immune reconstitution and protecting patients from life-threatening infections [5].

Other names

Adenosine aminohydrolaseADA1Adenosine deaminase 1

Restoration of enzymatic activity to catalyze the conversion of toxic deoxyadenosine to non-toxic deoxyinosine, thereby preventing the accumulation of dATP and allowing for normal lymphocyte development.