Influence of glucose fluctuations on alkaline phosphatase activity

It has been suggested previously that non-enzymatic glycosylation of certain enzymes results in decreased enzymatic activity. In order to examine the role of high blood glucose concentrations (BG) on serum alkaline phosphatase (AP) activity, we determined BG and serum AP in 32 healthy children during an oral glucose tolerance test (OGTT) and in 10 type I diabetic children at 30-min intervals for at least 150 min. A significant negative correlation was noted for BG and AP during the oral glucose load (r = -0.57, p less than 0.01). In diabetics, however, only children with marked BG fluctuations showed this inverse relationship between BG and AP. These observations could be explained by the formation of a Schiff base as the initial step of non-enzymatic glycosylation of AP. This assumption was further confirmed by in vitro experiments, in which AP was incubated with glucose resulting in decreased enzymatic activity. The dialyzable aldimine formed initially is subsequently stabilized as ketoamine after long-term incubation.