Kinetic analysis of glycation as a tool for assessing the half-life of proteins.
Glycation of proteins, a common postribosomal modification, proceeds via Amadori rearrangement to yield a stable ketoamine linkage of glucose with the protein. Kinetic analysis of the reaction shows that the amount of glycation at steady state is proportional to the glucose concentration, to protein half-life and to the rate of glycation. Thus, when the rate of glycation is determined in vitro and the extent of glycation of a given protein isolated from euglycemic subjects is measured, the half-life may be calculated. As the in vivo situation may not be simulated accurately in vitro, the calculated values may be considered as approximation. When the calculated values were compared with values reported in the literature fairly good agreement was found except for hemoglobin. Studies on stability of glycated albumin show that ketoamine decreases by about 20% when incubated under physiological conditions for 20 days. The method described by us is especially valuable when turnover of proteins in normal and pathophysiological states are compared. The half-life of plasma low-density lipoprotein is longer in patients with hypothyroidism or a high plasma low-density lipoprotein level than in normal subjects. Extending our studies to tissue proteins we did not find a significant increase in half-life of tendon collagen with age. Basement membrane collagen turnover is faster in diabetic patients in bad metabolic control. Thus, the procedure using fructosylamine as endogenous label of protein offers a method of great potential to study the turnover of human body proteins.
D000375:Aging; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008956:Models, Chemical; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism
D001798:Blood Proteins; D011506:Proteins; D012709:Serum Albumin