Abstract
The genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase lead to blocks in the purine pathway. The intracellular accumulation of deoxynucleosides and deoxynucleotides is toxic to both dividing and nondividing lymphocytes via multiple mechanisms. T-lymphocytes are uniquely sensitive to purine-mediated cytotoxicity because of a functional imbalance of phosphorylating and dephosphorylating enzymatic activities. These inborn errors or purine metabolism are rare disorders. The study of these conditions, however, has uncovered unique enzymatic properties of lymphocytes and lymphocyte subclasses. A better understanding of the mechanisms of lymphocytotoxicity in these two purine enzyme defects may lead to better modes of therapeutic manipulation of the immune system.
MeSH terms
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Adenosine Deaminase / deficiency
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Cytotoxicity, Immunologic
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Deoxyadenine Nucleotides / metabolism
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Deoxyadenosines / metabolism
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Deoxyguanine Nucleotides / metabolism
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Humans
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Immunologic Deficiency Syndromes / complications*
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Immunologic Deficiency Syndromes / etiology
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Immunologic Deficiency Syndromes / immunology
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Lymphocytes / immunology
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Lymphocytes / metabolism
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Purine-Nucleoside Phosphorylase / deficiency
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Purine-Pyrimidine Metabolism, Inborn Errors / complications*
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Purine-Pyrimidine Metabolism, Inborn Errors / etiology
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Purine-Pyrimidine Metabolism, Inborn Errors / immunology
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Purines / metabolism
Substances
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Deoxyadenine Nucleotides
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Deoxyadenosines
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Deoxyguanine Nucleotides
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Purines
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deoxyguanosine triphosphate
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Purine-Nucleoside Phosphorylase
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Adenosine Deaminase
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2'-deoxyadenosine triphosphate