title: Inhibition of 6-phosphogluconate dehydrogenase by carbamylation and protection by alpha-crystallin, a chaperone-like protein.
abstract: Carbamylation of lens proteins may contribute to cataract formation in populations with high levels of blood urea. Urea comes to equilibrium with cyanate. Changes induced by cyanate binding to lens crystallin have been described but little is known about the carbamylation of the enzymes. The present study investigated the in vitro carbamylation of 6-phospho-D-gluconate dehydrogenase (E.C.1.1.1.44) and its effect on the enzymic activity, as well as a possible way to prevent the cyanate binding to the enzyme. The covalent cyanate binding to protein inactivated the enzyme in a concentration-dependent fashion. Aspirin and paracetamol did not protect the enzyme against inactivation by carbamylation, while alpha-crystallin was specifically protective as compared with other control proteins, consistent with its suggested role as a molecular chaperone.
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Ganea
authors.forename: J J
authors.initials: JJ
authors.lastname: Harding
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002417:Cattle; D018833:Chaperonins / Q000494:pharmacology*; D003459:Crystallins / Q000494:pharmacology*; D003485:Cyanates / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000201:enzymology; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D009113:Muramidase / Q000494:pharmacology; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000302:isolation & purification; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000494:pharmacology
chemical_list: D002250:Carbon Radioisotopes; D003459:Crystallins; D003485:Cyanates; D012710:Serum Albumin, Bovine; D000082:Acetaminophen; D010734:Phosphogluconate Dehydrogenase; D009113:Muramidase; D018833:Chaperonins; C024835:potassium cyanate; D001241:Aspirin