Identification and characterization of mitochondrial factors modulating thymidine kinase 2 activity.
Thymidine kinase 2 (TK2) is one of four deoxynucleoside kinases (dNKs) in humans and plays a crucial role in the initial phosphorylation of pyrimidine nucleosides in the salvage pathway in mitochondria. Nucleoside analogues, like AZT, are substrates of TK2 and induced mitochondrial toxicity in long-term therapy. We found that AZT and FLT inhibited dThd phosphorylation but stimulated dCyd phosphorylation catalyzed by TK2. However, mitochondrial phosphorylation of both dThd and dCyd was inhibited by AZT and FLT. Here a preliminary identification and characterization of mitochondrial factors is reported.
Sun
R
R
Department of Anatomy, Section of Veterinary Medical Biochemistry, SLU, The Biomedical Centre, Uppsala, Sweden. sunmartin1983@hotmail.com
Eriksson
S
S
Wang
L
L
D000818:Animals; D002850:Chromatography, Gel; D003841:Deoxycytidine / Q000378:metabolism; D015224:Dideoxynucleosides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism*; D015215:Zidovudine / Q000494:pharmacology
D015224:Dideoxynucleosides; D011994:Recombinant Proteins; D003841:Deoxycytidine; D015215:Zidovudine; C105339:thymidine kinase 2; D013937:Thymidine Kinase; C002854:alovudine; D013936:Thymidine