Transport of Methionine Hydroxy Analog across the Brush Border Membrane of Rat Jejunum

Abstract

Brush border membrane vesicles and everted rings of rat jejunum were used to study the absorption of 2-hydroxy-4-methylthiobutyric acid, the α-hydroxy analog of methionine (DL-MHA). Uptake by membrane vesicles was found to be unaltered by an inwardly directed sodium gradient in contrast to that of L-methionine, D-methionine and L-lactate, which is sodium stimulated and exhibits a characteristic “overshoot” phenomenon. Initial uptake rates of both D- and D-methionine (0.77 mM) were respectively 6.8 and 1.5 times higher than that of DL-MHA (0.80 mM) under Na⁺-gradient conditions. However, the hydroxy analog significantly inhibited L-lactate accumulation into membrane vesicles. Uptake of DL-MHA into rat jejunal rings was the sum of a saturable Michaelian component [K^app_M = 4.4 mM and V^app_max = 587 nmol/(g·min)] and a diffusive component [K_d = 47 µL/(g·min)]. Furthermore, L-lactate completely inhibited the carrier-mediated uptake of DL-MHA. All this demonstrates that jejunal uptake of DL-MHA in the rat is mediated by an Na⁺-Independent carrier system associated with L-lactate transport and thus is quite distinct from the L-methionine pathway. This difference could help explain numerous findings with respect to a lower biological utilization of the hydroxy analog in some species when fed as the sole source of methionine in purified crystalline amino acid diets.