In PNP and ADA deficiencies the abnormalities observed in intracellular deoxynucleotide levels are more severe than in the corresponding ribose derivatives. These observations indicate selective roles for ADA and PNP in adenine and guanine deoxynucleotide degradation as compared to the corresponding ribonucleotide catabolism. We have found that distinct pathways are used for the catabolism of these purine deoxynucleotides and ribonucleotides. Thus, while adenine ribonucleotides are deaminated primarily by adenylate deaminase, adenine deoxynucleotides are exclusively deaminated by adenosine deaminase, explaining the specific impairment of adenine deoxynucleotide catabolism observed in ADA deficiency. In parallel, two distinct catabolic pathways exist for guanine nucleotide and deoxynucleotide degradation, while guanine ribonucleotide deamination proceed primarily through guanylate reductase to IMP, guanine deoxyribo-nucleotides are exclusively dephosphorylated to deoxyguanosine and then phosphorylized by PNP to guanine. These observations emphasized the importance of ADA and PNP not only in nucleotide degradation but primarily in the conversion of purine deoxyribonucleotides to their corresponding ribonucleotide derivatives through the active purine nucleoside cycles. The apparent activities of the catabolic enzymes adenosine deaminase, adenylate deaminase and purine nucleoside phosphorylase as well as the purine nucleoside cycle change markedly in the course of human T-lymphocyte differentiation.
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