title: Increased protein glycation in fructosamine 3-kinase-deficient mice.
abstract: Amines, including those present on proteins, spontaneously react with glucose to form fructosamines in a reaction known as glycation. In the present paper, we have explored, through a targeted gene inactivation approach, the role of FN3K (fructosamine 3-kinase), an intracellular enzyme that phosphorylates free and protein-bound fructose-epsilon-lysines and which is potentially involved in protein repair. Fn3k-/- mice looked healthy and had normal blood glucose and serum fructosamine levels. However, their level of haemoglobin-bound fructosamines was approx. 2.5-fold higher than that of control (Fn3k+/+) or Fn3k+/- mice. Other intracellular proteins were also significantly more glycated in Fn3k-/- mice in erythrocytes (1.8-2.2-fold) and in brain, kidney, liver and skeletal muscle (1.2-1.8-fold), indicating that FN3K removes fructosamines from intracellular proteins in vivo. The urinary excretion of free fructose-epsilon-lysine was 10-20-fold higher in fed mice compared with mice starved for 36 h, and did not differ between fed Fn3k+/+ and Fn3k-/- mice, indicating that food is the main source of urinary fructose-epsilon-lysine in these mice and that FN3K does not participate in the metabolism of food-derived fructose-epsilon-lysine. However, in starved animals, the urinary excretion of fructose-epsilon-lysine was 2.5-fold higher in Fn3k-/- mice compared with Fn3k+/+ or Fn3k+/- mice. Furthermore, a marked increase (5-13-fold) was observed in the concentration of free fructose-epsilon-lysine in tissues of fed Fn3k-/- mice compared with control mice, indicating that FN3K participates in the metabolism of endogenously produced fructose-epsilon-lysine. Taken together, these data indicate that FN3K serves as a protein repair enzyme and also in the metabolism of endogenously produced free fructose-epsilon-lysine.
authors.affiliation: Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Veiga da-Cunha
authors.forename: Patrick
authors.initials: P
authors.lastname: Jacquemin
authors.forename: Ghislain
authors.initials: G
authors.lastname: Delpierre
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfraind
authors.forename: Ivan
authors.initials: I
authors.lastname: Théate
authors.forename: Didier
authors.initials: D
authors.lastname: Vertommen
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clotman
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lemaigre
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Emile
authors.initials: E
authors.lastname: Van Schaftingen
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D005091:Exons / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006454:Hemoglobins / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D006454:Hemoglobins; D010455:Peptides; C033186:fructosyl-lysine; D017853:Phosphotransferases (Alcohol Group Acceptor); C414347:fructosamine-3-kinase; D008239:Lysine