Regulation of human erythrocyte glyceraldehyde-3-phosphate dehydrogenase by ferriprotoporphyrin IX.
Erythrocyte glyceraldehyde-3-phosphate dehydrogenase (G3PD) is a glycolytic enzyme containing critical thiol groups and whose activity is reversibly inhibited by binding to the cell membrane. Here, we demonstrate that the insertion of ferriprotoporphyrin IX (FP) into the red cell membranes exerts two opposite effects on membrane bound G3PD. First, the enzyme is partially inactivated through oxidation of critical thiols. Dithiothreitol restores part of the activity, but some critical thiols are irreversibly oxidized or crosslinked to products of FP-induced lipid peroxidation. Second, G3PD binding to the membrane is modified and the enzyme is activated through displacement into the cytosol and/or release from its binding site.
Omodeo Salè
Fausta
F
Institute of General Physiology and Biochemistry G. Esposito, Facoltá di Farmacia, University of Milan, Milan, Italy. fausta.omodeosale@unimi.it
Vanzulli
Elisa
E
Caielli
Simone
S
Taramelli
Donatella
D
D002462:Cell Membrane / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000201:enzymology; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D011485:Protein Binding; D013438:Sulfhydryl Compounds / Q000737:chemistry
D013438:Sulfhydryl Compounds; D006427:Hemin; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)