TY - JOUR
T1 - pH dependence of the inhibition of yeast glyoxalase I by porphyrins
AU - Douglas, Kenneth T.
AU - Sharif, Javad Ghotb
PY - 1983/10/28
Y1 - 1983/10/28
N2 - A number of porphyrin derivatives have been found to inhibit yeast glyoxalse I (EC 4.4.1.5) at 25°C, including haemin, protporphyrin 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 pIapp 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)glutatione was pH-independent. A detailed analysis of porphyrin binding modes was undertaken.
AB - A number of porphyrin derivatives have been found to inhibit yeast glyoxalse I (EC 4.4.1.5) at 25°C, including haemin, protporphyrin 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 pIapp 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)glutatione was pH-independent. A detailed analysis of porphyrin binding modes was undertaken.
KW - yeast
KW - glyoxalase inhibition
KW - porphyrin binding
KW - porphyrin derivative
UR - http://www.scopus.com/inward/record.url?scp=0021114503&partnerID=8YFLogxK
U2 - 10.1016/0167-4838(83)90294-7
DO - 10.1016/0167-4838(83)90294-7
M3 - Article
C2 - 6354270
AN - SCOPUS:0021114503
SN - 0167-4838
VL - 748
SP - 184
EP - 193
JO - Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
JF - Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
IS - 2
ER -