cDNA and amino acid sequence of human adenosine deaminase.

Human adenosine deaminase (ADA) is a purine catabolic enzyme that catalyzes the irreversible hydrolytic deamination of adenosine and deoxyadenosine. The enzyme is broadly distributed in human tissues with highest activity in lymphoid Adenosine deaminase purified from human erythrocytes is a soluble monomeric protein with an estimated molecular weight of about 38,000 daltons that exhibits post-translational modification."' In all tissues the enzyme is encoded for by a single genetic locus on the long arm of chromosome 20.&' An inherited deficiency of adenosine deaminase in its most extreme form is associated with an autosomal recessive form of severe combined immunodeficiency disease (SCID).' Patients have severe T cell and variable B cell dysfunction. In the absence of ADA activity, immature T cells selectively accumulate and are sensitive to dATP and deoxyadenosine toxicity. Patients have recurrent severe infections that usually become fatal within the first few years of life? These patients have undetectable enzyme activity in their erythrocytes and residual lymphocytes, but may have variable amounts of ADA enzymatic activity and immunoreactive protein in other tissues." As evidence for genetic heterogeneity in human ADA deficiency, a smaller group of partially ADA-deficient subjects have been identified through a genetic screening program or by serendipity. Subjects have undetectable ADA activity in senescent erythrocytes but 1-20% of normal lymphocyte enzyme activity."-" The partial ADA lymphocyte activity apparently protects these individuals against immunodeficiency and they remain healthy. Transformed B lymphoblast cell lines derived from these partially ADA-deficient individuals show characteristically low enzyme activity and structural mutations in the enzyme associated with electrophoretically alteredI3 or heat-labile ADA protein." Recent studies by Hutton and associates have described an elevated level of ADA mRNA in a B lymphoblast cell line derived from a severely and a partially ADA-deficient The mutation in both cases may be associated with an unstable ADA protein.