Methylamine osmoregulatory solutes of elasmobranch fishes counteract urea inhibition of enzymes

Abstract The intracellular fluids of marine elasmobranchs contain a set of methylamine compounds (trimethylamine oxide, betaine, and sarcosine) which are able to counteract the perturbing effects of urea on enzyme function (apparent Michaelis constant (K m ) and maximal velocity). The counteracting effects of the methylamine compounds and urea are maximal at a 2:1 ratio [urea]:[methylamines]. This is the same concentration ratio for these osmolytes found in the cells of marine elasmobranchs, holocephalans, and the coelacanth. The counteracting effects of the methylamine solutes and urea are observed with enzymes from non‐elasmobranchs as well as elasmobranchs, indicating that the enzymes of elasmobranchs are not specially adapted to function in the presence of urea or the methylamine osmolytes. Rather, the effects of urea and the methylamines on enzymes probably reflect fundamental protein‐solute interactions. The urea tolerance conferred by the methylamine solutes may have played an important role in elasmobranch evolution. The relief from urea perturbation afforded by these methylamines may have precluded the requirement for widespread modifications in the sequences of elasmobranch proteins to allow these proteins to function in the presence of perturbing urea concentrations.