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

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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 [KappM = 4.4 mM and Vappmax = 587 nmol/(g·min)] and a diffusive component [Kd = 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.

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