pH Dependence of the inhibition of yeast glyoxalase I by porphyrins.
A number of porphyrin derivatives have been found to inhibit yeast glyoxalase I (EC 4.4.1.5) at 25 degrees C, including haemin, protoporphyrin IX, coproporphyrin III, haematoporphyrin, deuteroporphyrin as well as meso-(tetrasubstituted) porphines. Bilirubin and chlorophyllin were also inhibitory, but not cobalamin, adipic, pimelic or suberic acids. Whilst the Ki value for linear competitive inhibition by meso-tetra(4-methylpyridyl)porphine was pH-dependent, analogous Ki values for meso-tetra(4-carboxyphenyl)- and meso-tetra(4-sulphonatophenyl)porphines followed the Henderson-Hasselbalch equation with pKapp values of 7.10 and 6.50, respectively. Protoporphyrin showed similar behaviour (pKapp 7.06) with a deviation at lower pH. The haemin pH profile for Ki showed a maximum at approx. pH 6.5. The redox reaction between haemin and glutathione did not interfere in the inhibition studies. The Ki value for S-(p-bromobenzyl)glutathione was pH-independent. A detailed analysis of porphyrin binding modes was undertaken.
D005978:Glutathione / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D008190:Lyases / Q000037:antagonists & inhibitors*; D011166:Porphyrins / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship
D011166:Porphyrins; D008190:Lyases; D007791:Lactoylglutathione Lyase; D005978:Glutathione