Enzymatic deglycation--a new paradigm or an epiphenomenon?
Following the discovery of FN3K (fructosamine 3-kinase), and more recently of FN3KRP (FN3K-related protein), research in our laboratory has been focused on testing the enzymatic deglycation hypothesis and investigating the roles of FN3K and FN3KRP. Thus far, using human erythrocytes as a model system, we have obtained the following evidence of enzymatic deglycation: (a) production of GHb (glycated haemoglobin) by D-glucose in intact erythrocytes is 5-fold lower than in haemolysates; (b) glycation of GHb by D-glucose in intact erythrocytes is 5-fold lower than that by L-glucose; (c) inhibition of ATP production in erythrocytes leads to an acceleration in the rate of GHb production by D-glucose; and (d) inhibition of FN3K in erythrocytes by a competitive inhibitor increases the accumulation of GHb. In spite of these data supporting the enzymatic deglycation hypothesis, some outstanding issues remain. These include, among others, the fact that while the apparent deglycation mechanism does not operate on L-glucose, semi-purified FN3K appears to be able to use both D- and L-fructosamines as substrates. Moreover, analysis of the fructoselysine 3-phosphate content of haemoglobin from diabetic subjects suggests that, in addition to FN3K, another deglycating mechanism may be operative in human erythrocytes. Elucidation of these issues is a challenge in the evolving field of deglycation research. Most important, however, is the question of whether enzymatic deglycation is truly an important defence mechanism or merely an epiphenomenon.
Szwergold
B S
BS
Department of Medicine, Dartmouth Medical School, Vail 212, HB 7515, Hanover, NH 03755, U.S.A. Szwergold@dartmouth.edu
Beisswenger
P J
PJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D002846:Chromatography, Affinity; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D013237:Stereoisomerism
D000255:Adenosine Triphosphate; D005947:Glucose; D006442:Glycated Hemoglobin; D017853:Phosphotransferases (Alcohol Group Acceptor); C414347:fructosamine-3-kinase