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.
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.
Robbins
B L
BL
Department of Infectious Disease, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. brian.robbins@stjude.org
Greenhaw
J
J
Fridland
A
A
D000263:Adenylate Kinase / Q000378:metabolism*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism*; D003838:Deoxyadenine Nucleotides / Q000737:chemistry / Q000378:metabolism*; D016049:Didanosine / Q000737:chemistry / Q000378:metabolism*; D054306:Dideoxynucleotides; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D010766:Phosphorylation; D013347:Subcellular Fractions; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D019380:Anti-HIV Agents; D003838:Deoxyadenine Nucleotides; D054306:Dideoxynucleotides; D007527:Isoenzymes; D013439:Sulfhydryl Reagents; C010110:2',3'-dideoxyadenosine 5'-phosphate; D000263:Adenylate Kinase; D016049:Didanosine