Abstract
Fructosamine 3-kinase (FN3K) and FN3K-related protein (FN3K-RP) catalyze the phosphorylation of the Amadori products ribulosamines, psicosamines, and, in the case of FN3K, fructosamines. BLAST searches in chordate genomes revealed two genes encoding proteins homologous to FN3K or FN3K-RP in various mammals and in chicken but only one gene, encoding a protein more similar to FN3K-RP than to FN3K, in fishes and the sea squirt Ciona intestinalis. This suggests that a gene duplication event occurred after the fish radiation and that the FN3K gene evolved more rapidly than the FN3K-RP gene. In agreement with this distribution, only one enzyme, phosphorylating ribulosamines and psicosamines but not fructosamines, was found in the tissues from a fish (Clarias gariepinus), whereas two enzymes with specificities similar to either FN3K or FN3K-RP were found in mouse, rat, and chicken tissues. FN3K is particularly active in brain, heart, kidney, and skeletal muscle. Its activity is also relatively elevated in erythrocytes from man, rat, and mouse but barely detectable in erythrocytes from chicken and pig, which correlates well with the low intracellular concentration of glucose in erythrocytes from these species. This is in keeping with the specific role of FN3K to repair protein damage caused by glucose. FN3K-RP was more evenly distributed in tissues, except for skeletal muscle where its activity was particularly low. This may be related to low activity of the pentose phosphate pathway in this tissue, as suggested by assays of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. This finding, together with the high affinity of FN3K-RP for ribulosamines, suggests that this enzyme may serve to repair damage caused by the powerful glycating agent, ribose 5-phosphate.
Highlights
Lian enzymes that phosphorylate ketoamines on the third carbon of their sugar moiety (1– 4)
Both Fructosamine 3-kinase (FN3K) and FN3K-related protein (FN3K-RP) phosphorylate ribulosamines and psicosamines, the glycation products of ribose and allose, but only the former catalyzes the phosphorylation of fructosamines, which are derived from glucose and are well known to be formed in animal tissues
Evolution of the FN3K Gene—We show in the present work that two distinct but related genes encoding orthologs of FN3K and FN3K-RP are present in the mammalian and chicken genomes, whereas there is only one FN3K/FN3K-RP homolog in the genomes of two fishes and of the urochordate C. intestinalis
Summary
Lian enzymes that phosphorylate ketoamines on the third carbon of their sugar moiety (1– 4). Ketoamines are produced through a spontaneous reaction of aldoses or aldose derivatives with an amine, followed by an Amadori rearrangement (5, 6). Both FN3K and FN3K-RP phosphorylate ribulosamines and psicosamines, the glycation products of ribose and allose, but only the former catalyzes the phosphorylation of fructosamines, which are derived from glucose and are well known to be formed in animal tissues. Evidence for the involvement of FN3K in the removal of fructosamines from hemoglobin and of FN3K-RP in the removal of ribulosamines and psicosamines has been obtained by incubating erythrocytes in the presence of elevated concentrations of glucose, ribose, or allose with or without competitive inhibitors of the two enzymes (7, 8). As FN3K might prevent some damaging effects of glucose, it was decided to test the effect of starvation and diabetes on the expression of this enzyme
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