Biochemical genetic analysis of 2',3'-dideoxyadenosine metabolism in human T lymphocytes.

Abstract

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.

• Authors: D A Carson, T Haertle, D B Wasson, D D Richman
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 151 Issue 2 Pg. 788-93 (Mar 15 1988) ISSN: 0006-291X [Print] United States
• PMID: 3258154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Deoxyadenosines
• Dideoxyadenosine
• Hypoxanthine Phosphoribosyltransferase
• Adenosine Kinase
• Deoxycytidine Kinase

Topics

• Adenosine Kinase (genetics)
• Antiviral Agents (metabolism)
• Cell Line
• Deoxyadenosines (analogs & derivatives, metabolism)
• Deoxycytidine Kinase (genetics)
• Dideoxyadenosine
• Humans
• Hypoxanthine Phosphoribosyltransferase (genetics)
• Monocytes (metabolism)
• Mutation
• T-Lymphocytes (metabolism)