Urea and methylamines have similar effects on aldose reductase activity

The concentration of urea in renal medullary cells is sufficiently high to inhibit activity of many enzymes, yet the cells survive and function. The generally accepted explanation is the counteracting osmolytes hypothesis, which holds that methylamines, such as glycerophosphorylcholine (GPC) and glycine betaine (betaine), found in the renal medulla stabilize biological macromolecules and oppose the effects of urea. The present study tests this hypothesis by determining the effects of urea and methylamines, singly and in combination, on the activity of aldose reductase, an enzyme that is important in renal medullas for catalyzing production of sorbitol from glucose. In apparent contradiction to the counteracting osmolytes hypothesis, urea (1.0 M) and three different methylamines (trimethylamine N-oxide, betaine, and GPC; 0.5 M) all have similar and partially additive inhibitory effects. They all decrease substantially both the Michaelis constant (K m) and the maximum velocity (V max). Also, a high concentr...