%0 Journal Article %1 Buchholz.200801 %A Buchholz, Kathrin %A Schirmer, Heiner R. %A Eubel, K. Jana %A Akoachere, B. Monique %A Dandekar, Thomas %A Becker, Katja %A Gromer, Stephan %D 2008/01// %J Antimicrob Agents Chemother %K Aerobiosis Animals Binding_Sites Disulfides Humans Hydrogen-Ion_Concentration IFZ Kinetics Methylene_Blue Oxidation-Reduction Oxidoreductases Plasmodium_falciparum Protozoan_Proteins Substrate_Specificity %N 1 %P 183-191 %T Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum %V 52 %X Methylene blue (MB) has experienced a renaissance mainly as a component of drug combinations against Plasmodium falciparum malaria. Here, we report biochemically relevant pharmacological data on MB such as rate constants for the uncatalyzed reaction of MB at pH 7.4 with cellular reductants like NAD(P)H (k = 4 M(-1) s(-1)), thioredoxins (k = 8.5 to 26 M(-1) s(-1)), dihydrolipoamide (k = 53 M(-1) s(-1)), and slowly reacting glutathione. As the disulfide reductases are prominent targets of MB, optical tests for enzymes reducing MB at the expense of NAD(P)H under aerobic conditions were developed. The product leucomethylene blue (leucoMB) is auto-oxidized back to MB at pH 7 but can be stabilized by enzymes at pH 5.0, which makes this colorless compound an interesting drug candidate. MB was found to be an inhibitor and/or a redox-cycling substrate of mammalian and P. falciparum disulfide reductases, with the kcat values ranging from 0.03 s(-1) to 10 s(-1) at 25 degrees C. Kinetic spectrosco

@article{Buchholz.200801, abstract = {Methylene blue (MB) has experienced a renaissance mainly as a component of drug combinations against Plasmodium falciparum malaria. Here, we report biochemically relevant pharmacological data on MB such as rate constants for the uncatalyzed reaction of MB at pH 7.4 with cellular reductants like NAD(P)H (k = 4 M(-1) s(-1)), thioredoxins (k = 8.5 to 26 M(-1) s(-1)), dihydrolipoamide (k = 53 M(-1) s(-1)), and slowly reacting glutathione. As the disulfide reductases are prominent targets of MB, optical tests for enzymes reducing MB at the expense of NAD(P)H under aerobic conditions were developed. The product leucomethylene blue (leucoMB) is auto-oxidized back to MB at pH 7 but can be stabilized by enzymes at pH 5.0, which makes this colorless compound an interesting drug candidate. MB was found to be an inhibitor and/or a redox-cycling substrate of mammalian and P. falciparum disulfide reductases, with the kcat values ranging from 0.03 s(-1) to 10 s(-1) at 25 degrees C. Kinetic spectrosco}, added-at = {2008-10-14T16:07:18.000+0200}, author = {Buchholz, Kathrin and Schirmer, Heiner R. and Eubel, K. Jana and Akoachere, B. Monique and Dandekar, Thomas and Becker, Katja and Gromer, Stephan}, biburl = {https://www.bibsonomy.org/bibtex/26df645811ef0bb6960d1c47ce69d8409/nutribiochem}, interhash = {87286afedf7c4a5ce32c7f9abbc27d55}, intrahash = {6df645811ef0bb6960d1c47ce69d8409}, journal = {Antimicrob Agents Chemother}, keywords = {Aerobiosis Animals Binding_Sites Disulfides Humans Hydrogen-Ion_Concentration IFZ Kinetics Methylene_Blue Oxidation-Reduction Oxidoreductases Plasmodium_falciparum Protozoan_Proteins Substrate_Specificity}, number = 1, pages = {183-191}, timestamp = {2008-10-14T16:08:41.000+0200}, title = {Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum}, volume = 52, year = {2008/01//} }