title: Fructosamine 3-kinase-related protein and deglycation in human erythrocytes.
abstract: Fructosamine 3-kinase (FN3K), an enzyme initially identified in erythrocytes, catalyses the phosphorylation of fructosamines on their third carbon, leading to their destabilization and their removal from protein. We show that human erythrocytes also contain FN3K-related protein (FN3K-RP), an enzyme that phosphorylates psicosamines and ribulosamines, but not fructosamines, on the third carbon of their sugar moiety. Protein-bound psicosamine 3-phosphates and ribulosamine 3-phosphates are unstable, decomposing at pH 7.1 and 37 degrees C with half-lives of 8.8 h and 25 min respectively, as compared with 7 h for fructosamine 3-phosphates. NMR analysis indicated that 1-deoxy-1-morpholinopsicose (DMP, a substrate for FN3K and FN3K-RP), like 1-deoxy-1-morpholinofructose (DMF, a substrate of FN3K), penetrated erythrocytes and was converted into the corresponding 3-phospho-derivative. Incubation of erythrocytes with 50 mM allose, 200 mM glucose or 10 mM ribose for 24 h resulted in the accumulation of glycated haemoglobin, and this accumulation was approx. 1.9-2.6-fold higher if DMP, a competitive inhibitor of both FN3K and FN3K-RP, was present in the incubation medium. Incubation with 50 mM allose or 200 mM glucose also caused the accumulation of ketoamine 3-phosphates, which was inhibited by DMP. By contrast, DMF, a specific inhibitor of FN3K, only affected the glucose-dependent accumulation of glycated haemoglobin and ketoamine 3-phosphates. These data indicate that FN3K-RP can phosphorylate intracellular, protein-bound psicosamines and ribulosamines, thus leading to deglycation.
authors.affiliation: Laboratory of Physiological Chemistry, ICP and Université Catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Collard
authors.forename: Elsa
authors.initials: E
authors.lastname: Wiame
authors.forename: Niki
authors.initials: N
authors.lastname: Bergans
authors.forename: Juliette
authors.initials: J
authors.lastname: Fortpied
authors.forename: Didier
authors.initials: D
authors.lastname: Vertommen
authors.forename: Florent
authors.initials: F
authors.lastname: Vanstapel
authors.forename: Ghislain
authors.initials: G
authors.lastname: Delpierre
authors.forename: Emile
authors.initials: E
authors.lastname: Van Schaftingen
mesh_terms: D000588:Amines / Q000737:chemistry; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology*; D005632:Fructose / Q000031:analogs & derivatives* / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000737:chemistry; D006801:Humans; D007649:Ketamine / Q000737:chemistry; D009025:Morpholines / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000588:Amines; D005632:Fructose; D005947:Glucose; D006442:Glycated Hemoglobin; D007649:Ketamine; D009025:Morpholines; D010710:Phosphates; D017853:Phosphotransferases (Alcohol Group Acceptor); C044913:1-deoxy-1-morpholinofructose; C479999:FN3KRP protein, human