# name
Monocarboxylate transporter 1 mediates DL-2-hydroxy-(4-methylthio)butanoic acid transport across the apical membrane of Caco-2 cell monolayers.

# metadata.dc.description.abstract[].value
The methionine hydroxy analogue DL-2-hydroxy-(4-methylthio)butanoic acid (DL-HMB) is a supplementary source of methionine commonly

added to commercial animal diets to satisfy the total sulfur amino acid requirement. In this study, we characterized DL-HMB transport across

the apical membrane of Caco-2 cells to identify the transport mechanism involved in the intestinal absorption of this methionine source. DLHMB

transport induced a significant decrease in intracellular pH (pHi) and was inhibited in the presence of the protonophore carbonyl cyanide 4-

(trifluoromethoxy)-phenylhydrazone. Moreover, both Na1 removal and 5-(N-ethyl-N-isopropyl)amiloride, an inhibitor of apical Na1/H1 exchanger

(NHE3), significantly reduced substrate uptake and pHi recovery, suggesting cooperation between H1-dependent DL-HMB transport and NHE3

activity. cis-Inhibition experiments with L-Ala, b-Ala, D-Pro, betaine, or glycyl-sarcosine excluded the participation of systems proton amino acid

transporter 1 and peptide transporter 1. In contrast, a-cyano-4-hydroxycinnamate, phloretin, L-lactate, b-hydroxybutyrate, butyrate, and

pyruvate, inhibitors and substrates of monocarboxylate transporter 1 (MCT1), significantly reduced DL-HMB uptake. Dixon plot analysis of Llactate

transport in the presence of DL-HMB revealed a competitive interaction (inhibition constant, 17.5 6 0.11 mmol/L), confirming the

participation of system MCT1. The kinetics of DL-HMB uptake was described by a model involving passive diffusion and a single low-affinity,

high-capacity transport mechanism (KD, 1.9 nL/mg protein; Km, 13.16 0.04 mmol/L; and Vmax, 43.6 6 0.14 pmol/mg protein) compatible with

MCT1 kinetic characteristics. In conclusion, the methionine hydroxy analogue is transported in Caco-2 cell apical membrane by a transport

mechanism with functional characteristics similar to those of MCT1.

# metadata.dc.relation.isformatof[].value
Versió postprint del document publicat a:

# metadata.dc.rights[].value
(c) American Society for Nutrition, 2007

# metadata.dc.source[].value
Articles publicats en revistes (Bioquímica i Fisiologia)

# metadata.dc.title[].value
Monocarboxylate transporter 1 mediates DL-2-hydroxy-(4-methylthio)butanoic acid transport across the apical membrane of Caco-2 cell monolayers.