Cellular Phosphorylation of 2′, 3′-Dideoxyadenosine-5′-monophosphate, a Key Intermediate in The Activation of the Antiviral Agent DDI, in Human Peripheral Blood Mononuclear Cells

• Published in: Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2000-01, Vol.19 (1-2), p.405-413
• Main Authors: Robbins, Brian L., Greenhaw, Jack, Fridland, Arnold
• Format: Article
• Language: English
• Subjects: Adenylate Kinase - metabolism; AIDS/HIV; Anti-HIV Agents - chemistry; Anti-HIV Agents - metabolism; Deoxyadenine Nucleotides - chemistry; Deoxyadenine Nucleotides - metabolism; Didanosine - chemistry; Didanosine - metabolism; Dideoxynucleotides; Humans; In Vitro Techniques; Isoenzymes - metabolism; Leukocytes, Mononuclear - metabolism; Mitochondria - enzymology; Phosphorylation; Subcellular Fractions; Sulfhydryl Reagents - pharmacology; T-Lymphocytes - metabolism
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770008033017

2′,3′-dideoxyadenosine 5-monophosphate (ddAMP), is a key intermediate in the metabolism of the antiviral agent 2′,3′-dideoxyinosine (ddI) to its active triphosphate derivative, 2′,3′-dideoxyadenosine-5′-triphosphate (ddATP). The potential role of adenylate kinase in the phosphorylation of ddAMP was studied in human peripheral blood mononuclear cells (PBMC) and a human T cell line, CEMss. Subcellular distribution, sulfhydryl inhibitor, and substrate specificity studies support the hypothesis that the mitochondrial adenylate kinase (AK2) is a major route of cellular activation of these compounds in human lymphocytes.