Revival of inactive glyceraldehyde 3-phosphate dehydrogenase in human cataract lenses by reduction.
In this study, endogenous as well as synthetic reducing systems were shown to reduce the disulphide bonds formed in glyceraldehyde 3-phosphate dehydrogenase, an important glycolytic enzyme previously reported to have lost its activity in human cataract lenses, resulting in reviving the activity of this enzyme. Disulphide bond formation is a non-specific posttranslational modification of proteins, which leads to a loss of function of the affected protein. When an enzyme is targeted, this harmful effect can be easily detected by monitoring the change of activity. Endogenous reducing systems are responsible for breaking these bonds and returning the protein (enzyme) to its natural state, when these mechanisms fail to do so, the loss of enzyme activity will be permanent.
Rachdan
Diyaa
D
Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford OX2 6AW, UK.
Lou
Marjorie F
MF
Harding
John J
JJ
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002386:Cataract / Q000201:enzymology*; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D054477:Glutaredoxins; D005978:Glutathione / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology*; D008875:Middle Aged; D011490:Protein Disulfide Reductase (Glutathione) / Q000494:pharmacology; D019163:Reducing Agents / Q000494:pharmacology*; D013053:Spectrophotometry
D000806:Angiotensin-Converting Enzyme Inhibitors; D054477:Glutaredoxins; D019163:Reducing Agents; D002216:Captopril; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011490:Protein Disulfide Reductase (Glutathione); D005978:Glutathione; D004229:Dithiothreitol