期刊
BIOCHEMICAL JOURNAL
卷 399, 期 -, 页码 257-264出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20060684
关键词
diabetic complication; fructosamine 3-kinase (FN3K) inactivation; fructoselysine; glycated haemoglobin (GlcHb); intracellular glycation; protein repair
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 fructosammes 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-E-lysine in these mice and that FN3K does not participate in the metabolism of food-derived fructose-E-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.
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