Biochemical genetic analysis of 2',3'-dideoxyadenosine metabolism in human T lymphocytes.
2',3'-dideoxyadenosine (ddAdo) has been shown to inhibit the infection of cultured human T lymphoblasts with the human immunodeficiency virus-1 (HIV-1). However, the pathways of ddAdo metabolism in T lymphocytes have not been well defined. We have studied the uptake and degradation of ddAdo in human CEM T lymphoblasts, in mutant CEM T cells deficient in adenosine kinase or deoxycytidine kinase, and in normal lymphocytes and monocytes. The results indicate that ddAdo may be phosphorylated in T cells by several different enzymes, although deoxycytidine kinase predominates. However, 99% of the ddAMP formed is deaminated by AMP deaminase and subsequently dephosphorylated. Thus, the ability of ddAdo to prevent HIV-1 infection may be limited in cells with high AMP deaminase activity.
Carson
D A
DA
Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Haertle
T
T
Wasson
D B
DB
Richman
D D
DD
D000248:Adenosine Kinase / Q000235:genetics; D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000235:genetics; D016048:Dideoxyadenosine; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009000:Monocytes / Q000378:metabolism; D009154:Mutation; D013601:T-Lymphocytes / Q000378:metabolism*
D000998:Antiviral Agents; D003839:Deoxyadenosines; D016048:Dideoxyadenosine; D007041:Hypoxanthine Phosphoribosyltransferase; D000248:Adenosine Kinase; D003842:Deoxycytidine Kinase