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Ras-related C3 botulinum toxin substrate 1 Amidophosphoribosyltransferase Equilibrative nucleoside transporter 1 Sodium/nucleoside cotransporter 2 Equilibrative nucleoside transporter 2 Hypoxanthine- guanine phosphoribosyltransferase Thioguanosine 5'-triphosphate 6-Thioguanosine monophosphate Thioguanosine 5'-triphosphate 5-Phosphoribosylamine Thioguanine Thioguanine Thioguanine Phosphoribosyl pyrophosphate PPi Thioguanosine 5'-diphosphate Thiodeoxyguanosine 5'-diphosphate Thiodeoxyguanosine-5'- triphosphate L-Glutamine Phosphoribosyl pyrophosphate L-Glutamic acid PPi Na+ Na+ RNA Synthesis Regulation of Apoptosis of Activated T Cells Reference De novo purine synthesis Magnesium 4Fe-4S DNA synthesis Magnesium Cytosol Thioguanine is converted firstly, to its active form then to its monophosphate, diphosphate and, finally, its triphosphate forms in the nucleoside salvage pathway. T Cell Blood vessel T Cell Apoptosis The apoptosis of the T and B cells results in the death of the cancerous white blood cells but also ini the mmunosuppression of the patient by the death of the B and T cells and, also, by the arrest of antibodies production. Due to the inhibition of the DNA synthesis, the inhibition of the DNA polymerase, and the inhibition of the ribonucleoside reductase, the T and B cells will go through apoptosis.This drug cause cells to accumulate at the G1/S phase junction. Thioguanosine 5'-triphosphate accumulates and is incorporated in the DNA due to its structure. Nucleus The incorporation in the DNA results in DNA breaks and the inhibition of DNA synthesis and repair. During the replication of the DNA, this will cause the apoptosis of the T cells. The accumulation of thioguanosine 5'-triphosphate inhibits the glutamine-5- phosphoribosylpyrophosphate amidotransferase. This leads to an imbalance of purine ribonucleotides in the cell because it is the first enzyme in the de novo pathway of purine ribonucleotide synthesis. This will impact the DNA synthesis because the purine pool will be changed. The imbalanced purine pool leads to DNA strand breaks and to the inhibition of the DNA synthesis. Through depletion of the dNTP pool, clofarabine self-potentiates the incorporation of clofarabine triphosphates into DNA. Thioguanosine 5'-triphosphate can be incorporated into RNA creating unusable RNA that can't be translated into proteins. Thioguanosine 5'-triphosphate also inhibits ras-related C3 botulinum toxin substrate 1 which is a small GTPase membrane protein that regulates many cellular events such as proliferation, cell to cell adhesion, apoptosis and more. Most importantly it regulates the apoptosis of T and B lymphocytes. With it's inhibition, T and B lymphocytes undergo apoptosis causing immunosuppression. Thiodeoxyguanosine-5'- triphosphate can be incorporated into DNA. This creates unusable DNA that cannot be replicated or transcripted.
Nucleus RAC1 PPAT SLC29A1 SLC28A2 SLC29A2 HPRT1 Thioguanosine 5'-triphosphate 6-Thioguanosine monophosphate Thioguanosine 5'-triphosphate 5- Phosphoribosylamine Thioguanine Thioguanine Thioguanine Phosphoribosyl pyrophosphate Pyrophosphate Thioguanosine 5'-diphosphate Thiodeoxyguanosine 5'-diphosphate Thiodeoxyguanosine- 5'- triphosphate L-Glutamine Phosphoribosyl pyrophosphate L-Glutamic acid Pyrophosphate Sodium Sodium RNA Synthesis Regulation of Apoptosis of Activated T Cells Reference De novo purine synthesis DNA synthesis
RAC1 PPAT SLC29A1 SLC28A2 SLC29A2 HPRT1 ToGS5TP 6TgsMP ToGS5TP 5-PPRSA ThioGua ThioGua ThioGua PRPP PPi ToGS5DP ToDG5DP Th-5'-t Gln PRPP Glu PPi Na+ Na+ RNA Syn R o A o D n p s Mg2+ 4Fe-4S DNA syn Mg2+ Cytosol Thioguanine is converted firstly, to its active form then to its monophosphate, diphosphate and, finally, its triphosphate forms in the nucleoside salvage pathway. T Cell Blood vessel T Cell Apoptosis The apoptosis of the T and B cells results in the death of the cancerous white blood cells but also ini the mmunosuppression of the patient by the death of the B and T cells and, also, by the arrest of antibodies production. Due to the inhibition of the DNA synthesis, the inhibition of the DNA polymerase, and the inhibition of the ribonucleoside reductase, the T and B cells will go through apoptosis.This drug cause cells to accumulate at the G1/S phase junction. Thioguanosine 5'-triphosphate accumulates and is incorporated in the DNA due to its structure. Nucleus The incorporation in the DNA results in DNA breaks and the inhibition of DNA synthesis and repair. During the replication of the DNA, this will cause the apoptosis of the T cells. The accumulation of thioguanosine 5'-triphosphate inhibits the glutamine-5- phosphoribosylpyrophosphate amidotransferase. This leads to an imbalance of purine ribonucleotides in the cell because it is the first enzyme in the de novo pathway of purine ribonucleotide synthesis. This will impact the DNA synthesis because the purine pool will be changed. The imbalanced purine pool leads to DNA strand breaks and to the inhibition of the DNA synthesis. Through depletion of the dNTP pool, clofarabine self-potentiates the incorporation of clofarabine triphosphates into DNA. Thioguanosine 5'-triphosphate can be incorporated into RNA creating unusable RNA that can't be translated into proteins. Thioguanosine 5'-triphosphate also inhibits ras-related C3 botulinum toxin substrate 1 which is a small GTPase membrane protein that regulates many cellular events such as proliferation, cell to cell adhesion, apoptosis and more. Most importantly it regulates the apoptosis of T and B lymphocytes. With it's inhibition, T and B lymphocytes undergo apoptosis causing immunosuppression. Thiodeoxyguanosine-5'- triphosphate can be incorporated into DNA. This creates unusable DNA that cannot be replicated or transcripted.
Nucleus RAC1 PPAT SLC29A1 SLC28A2 SLC29A2 HPRT1 ToGS5TP 6TgsMP ToGS5TP 5-PPRSA ThioGua ThioGua ThioGua PRPP Ppi ToGS5DP ToDG5DP Th-5'-t Gln PRPP Glu Ppi Na+ Na+ RNA Syn R o A o D n p s DNA syn