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Rapid Publication Free access | 10.1172/JCI109058

Deoxyguanosine Triphosphate as a Possible Toxic Metabolite in the Immunodeficiency Associated with Purine Nucleoside Phosphorylase Deficiency

Amos Cohen, Lorraine J. Gudas, Arthur J. Ammann, Gerard E. J. Staal, and David W. Martin Jr.

Department of Medicine, University of California at San Francisco, San Francisco, California 94143

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143

Department of Pediatrics, University of California at San Francisco, San Francisco, California 94143

Department of Medical Enzymology, Academic Hospital, Utrecht, The Netherlands

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Department of Medicine, University of California at San Francisco, San Francisco, California 94143

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143

Department of Pediatrics, University of California at San Francisco, San Francisco, California 94143

Department of Medical Enzymology, Academic Hospital, Utrecht, The Netherlands

Find articles by Gudas, L. in: PubMed | Google Scholar

Department of Medicine, University of California at San Francisco, San Francisco, California 94143

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143

Department of Pediatrics, University of California at San Francisco, San Francisco, California 94143

Department of Medical Enzymology, Academic Hospital, Utrecht, The Netherlands

Find articles by Ammann, A. in: PubMed | Google Scholar

Department of Medicine, University of California at San Francisco, San Francisco, California 94143

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143

Department of Pediatrics, University of California at San Francisco, San Francisco, California 94143

Department of Medical Enzymology, Academic Hospital, Utrecht, The Netherlands

Find articles by Staal, G. in: PubMed | Google Scholar

Department of Medicine, University of California at San Francisco, San Francisco, California 94143

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143

Department of Pediatrics, University of California at San Francisco, San Francisco, California 94143

Department of Medical Enzymology, Academic Hospital, Utrecht, The Netherlands

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Published May 1, 1978 - More info

Published in Volume 61, Issue 5 on May 1, 1978
J Clin Invest. 1978;61(5):1405–1409. https://doi.org/10.1172/JCI109058.
© 1978 The American Society for Clinical Investigation
Published May 1, 1978 - Version history
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Abstract

Purine nucleoside phosphorylase (PNP) deficiency is associated with a severe defect in thymus-derived (T)-lymphocyte function combined with normal bone marrow-derived (B)-lymphocyte function. To investigate the role of this enzyme deficiency in the resulting immune dysfunction, we measured the levels of ribonucleoside and deoxyribonucleoside triphosphates in erythrocytes from two unrelated PNP-deficient, T-lymphocyte-deficient patients. Both PNP-deficient patients have abnormally high levels of deoxyguanosine triphosphate (deoxy-GTP) in their erythrocytes (5 and 8 nmol/ml packed erythrocytes). In contrast, normal controls and adenosine deaminase-deficient, immunodeficient patients do not have detectable amounts of deoxyGTP (<0.5 nmol/ml packed erythrocytes). We propose that deoxyguanosine, a substrate of PNP, is the potentially lymphotoxic metabolite in PNP deficiency. The mechanism of toxicity involves phosphorylation of deoxyguanosine to deoxyGTP, which acts as a potent inhibitor of mammalian ribonucleotide reductase.

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