Erythrocytes deoxyadenosine metabolism

D. Perrett, A. Sahota, H.A. Simmonds, and K.Hugh-Jones. Deoxyadenosine metabolism in the erythrocytes of children with severe, combined immunodeficiency. Bioscience Reports 1 933 (1981)... 

Szabados, E. Duggleby, R.G. Christopherson, R.I. Metabolism of adenosine and deoxyadenosine by human erythrocytes and CCRF-CEM leukemia cells. Int. J. Biochem. Cell Biol., 28, 1405-1414 (1996)... 

Adenosine (deoxyadenosine) is metabolized by erythrocytes (RBC) to either adenylates via adenylate kinase (AK) or to inosine by adenosine deaminase (ADA). Inosine, guanosine and their deoxy forms are converted to the purine base hypoxanthine by purine nucleoside phosphorylase (PNP). 

Congenital defects and chemical inhibitors of these enzymes result in the accumulation of purine nucleosides and nucleotides which have been directly linked to impaired lymphocyte function and immunodeficiency syndromes (4,5). Since the uremic state is complicated by an increased susceptability to infection largely the result of acquired l3nnphocyte abnormalities, we have studied the ability of uremic erythrocytes (RBC) to metabolize vitro radiolabelled adenosine and deoxyadenosine utilizying a combind UV - radioactive high performance liquid chromatographic technique (HPLC) (1,2,3). 

NUCLEOTIDE LEVELS AND METABOLISM OF ADENOSINE AND DEOXYADENOSINE IN INTACT ERYTHROCYTES DEFICIENT IN ADENOSINE DEAMINASE... 

Table 1. Metabolism of adenosine and deoxyadenosine in ADA deficient erythrocytes.

Evidence that purine metabolism is important in the immune response has been obtained from the observation that markedly reduced or absent adenosine deaminase (ADA) activity in man has been casually associated with an autosomal recessive form of severe combined immunodeficiency disease (3). Recently, ADA levels in lymphocytes from patients with untreated chronic lymphatic leukemia have been found to be consistently lower than in lymphocytes from normal subjects (4). Children with ADA deficiency and immunodeficiency have been shown to have increased levels in plasma, urine, lymphocytes and erythrocytes of adenosine, adenine, deoxy-adenosine, adenine nucleotides, and deoxyadenine (5, 6). Although the exact biochemical mechanism(s) is unknown, elevated levels of adenosine, and/or deoxyadenosine and their metabolites are thought to be selective inhibitors of both differentiation and effector function of lymphocytes (7, 8). Adenosine was known to inhibit the PHA-induced blastogenesis of human peripheral blood lymphocytes (9) even before the discovery of the first ADA-deficient child. In addition, elevated levels of cyclic AMP (cAMP) were known to be inhibitory for lymphocyte-mediated cytotoxicity (7). Since... 

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