Joy Y. Feng, Allison A. Johnson, Kenneth A. Johnson and Karen S. Anderson(2001)
Insights into the Molecular Mechanism of Mitochondrial Toxicity by
AIDS Drugs*
The Journal of Biological Chemistry Vol.276,No.26, Issue of June, pp.23832-23837
Insights into the Molecular Mechanism of Mitochondrial Toxicity by AIDS Drugs*
The Journal of Biological Chemistry Vol.276,No.26, Issue of June, pp.23832-23837
(Translated by Owais A. Shahzada)
Implications: Toxicity comparison
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In this table the two main things to take away is the kpol(rate of polymerization) and kd(tightness of binding). Two of the analogs are being compared to dCTP because it is the wild-type meaning it is the rate at which dna polymerase occurs at a normal mitochondrial DNA. The plus and minus for each of the numbers mean an approximation of for example (44 +- 2 = 42 or 44 seconds). (-) 3TC is shown to have a slower polymerization rate making it less toxic and notice that the tightness of binding is also a much weaker compared to (+)3TC. Both those reasons make it less toxic because (-)3TC does not incorporate well into the polymerase allowing DNA polymerase gamma to function.
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Fig. 7:Incorporation rate comparison of each nucleoside analog: The table is labeled with a header that contains dNTP indicated the types of nucleotide used in the experiment. Kpol for the rate of polymerization in miliseconds (s^-1) and Kss for the steady state in miliseconds(s^-1) |