The adenosine deaminase (ADA) metabolism

The adenosine deaminase (ADA) metabolism. ADA is an enzyme of the purine salvage pathway, which catalyzes the irreversible deamination of adenosine and 2′-deoxyadenosine into inosine and 2′-deoxyinosine, respectively. Most adenosine derives from endogenous breakdown of ATP and degradation of RNA, or is taken up exogenously by ubiquitously expressed nucleoside transporters. Unlike adenosine, 2′-deoxyadenosine is formed by DNA degradation is predominantly catabolized by ADA. Further conversion of inosine nucleoside leads to hypoxanthine, which can either enter a non-reversible pathway to uric acid or salvaged back into other mononucleosides. In the absence of ADA, the presence of these alternative “bypass” pathways results in normal concentrations of the catabolic products of the enzyme reaction in patients with ADA-SCID. Conversely, the levels of ADA substrates, adenosine and 2′-deoxyadenosine, are not only found in increased amounts in extracellular body fluids, but they also “spill over” into additional pathways normally only minimally utilized, thus contributing to the pathogenic mechanisms of the disease.

Publication

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency. (2012) Aisha Vanessa Sauer, et al. Front Immunol. 2012;3:265. Figure: F1. All organisms Homo sapiens Drosophila melanogaster

Disease mentions