Transport Mechanisms of the Large Neutral Amino Acid L-Phenylalanine in the Human Intestinal Epithelial Caco-2 Cell Line

Berger, Valérie; Larondelle, Yvan; Trouet, André; Schneider, Yves‐Jacques

doi:10.1093/jn/130.11.2780

Cited by 26 publications

(14 citation statements)

References 21 publications

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“…Once again, the results confirmed the interest in LNAA supplementation in the regulation of plasma Phe levels, most probably because of the competitive absorption of LNAA at the intestinal mucosa (Broer 2008). The competitive intestinal absorption of LNAA was verified using both rabbit and mouse intestinal tissue (Karasov et al 1986;Munck and Munck 1994;Stevens et al 1982) and human intestinal epithelial Caco-2 cells, where Phe and other LNAA were shown to compete for transport from the apical to the basolateral membrane (Berger et al 2000).…”

Section: Lnaa Supplementation In the Treatment Of Pku Patientssupporting

confidence: 70%

Large neutral amino acids supplementation in phenylketonuric patients

Rocha¹,

Martel

2009

J of Inher Metab Disea

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Phenylketonuria is an inborn error of amino acid metabolism that results in severe mental retardation if not treated early and appropriately. The traditional treatment, consisting of a low-phenylalanine diet, is usually difficult to maintain throughout adolescence and adulthood, resulting in undesirable levels of blood phenylalanine and consequent neurotoxicity. The neurotoxicity of phenylalanine is enhanced by its transport mechanism across the blood-brain barrier, which has the highest affinity for phenylalanine compared with the other large neutral amino acids that share the same carrier. The supplementation of large neutral amino acids in phenylketonuric patients has been showing interesting results. Plasma phenylalanine levels can be reduced, which may guarantee important metabolic and clinical benefits to these patients. Although long-term studies are needed to determine the efficacy and safety of large neutral amino acids supplements, the present state of knowledge seems to recommend their prescription to all phenylketonuric adult patients who are non-compliant with the low-phenylalanine diet.

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Section: Lnaa Supplementation In the Treatment Of Pku Patientssupporting

confidence: 70%

Large neutral amino acids supplementation in phenylketonuric patients

Rocha¹,

Martel

2009

J of Inher Metab Disea

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“…Nevertheless, a Na ϩ -independent transport component for neutral amino acids sensitive to BCH has been detected in the apical membrane of chicken, pig, and rabbit intestine (22,40,42). Moreover, Berger et al (1) reported that apical Na ϩ -independent L-phenylalanine uptake was mediated by systems b 0,ϩ and L in Caco-2 cells. Therefore, the results showing the inhibition of L-Met uptake by BCH in the absence of Na ϩ may confirm L activity across the apical membrane.…”

Section: Discussionmentioning

confidence: 99%

Effect of pH on l- and d-methionine uptake across the apical membrane of Caco-2 cells

Martín‐Venegas

Rodríguez-Lagunas²,

Mercier³

et al. 2009

American Journal of Physiology-Cell Physiology

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The transport systems involved in intestinal methionine (Met) absorption are described as Na ϩ -dependent and Na ϩ -independent mechanisms. However, since recent studies have suggested the importance of the H ϩ gradient as a driving force for intestinal nutrient absorption, the aim of the present work was to test whether Met transport across the apical membrane of Caco-2 cells is affected by extracellular pH. The results show that Land D-Met uptake was increased by lowering extracellular pH from 7.4 to 5.5, in both the presence and absence of Na ϩ . Cis-inhibition experiments revealed that inhibition of L-Met transport by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) or L-lysine (L-Lys) was higher at a pH of 5.5. Moreover, the BCH-insensitive component was not affected by pH, whereas the L-Lys-insensitive component was increased by lowering extracellular pH, thus suggesting the participation of system L. The contribution of another mechanism, sensitive to both BCH and L-Lys, was also considered. The inhibition obtained with taurine (Tau) was also higher at a pH of 5.5, thus suggesting the involvement of system B 0,ϩ on pH-stimulated component. As for D-Met uptake, the results showed higher inhibition with L-Lys and Tau at a pH of 5.5 and no effect on the L-Lys-or Tau-insensitive component. In conclusion, Met transport across the apical membrane of Caco-2 cells is increased by low extracellular pH as the result of the stimulation of two transport systems functionally identified with systems L and B 0,ϩ for L-Met and with system B 0,ϩ for D-Met.

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“…Amino acid transport has also been studied in monolayers of Caco-2 cells. The results indicate that carrier-mediated transport of amino acids is significantly faster than their paracellular transport (141,148) or the transport of D-mannitol, which occurs entirely by the paracellular route (25,26). These studies used low concentrations of radiolabeled amino acids and therefore may underestimate paracellular transport at higher concentrations.…”

Section: Significance Of Paracellular Transportmentioning

confidence: 93%

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

Bröer

2008

Physiological Reviews

831

671

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The transport of amino acids in kidney and intestine is critical for the supply of amino acids to all tissues and the homeostasis of plasma amino acid levels. This is illustrated by a number of inherited disorders affecting amino acid transport in epithelial cells, such as cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, dicarboxylic aminoaciduria, and some other less well-described disturbances of amino acid transport. The identification of most epithelial amino acid transporters over the past 15 years allows the definition of these disorders at the molecular level and provides a clear picture of the functional cooperation between transporters in the apical and basolateral membranes of mammalian epithelial cells. Transport of amino acids across the apical membrane not only makes use of sodium-dependent symporters, but also uses the proton-motive force and the gradient of other amino acids to efficiently absorb amino acids from the lumen. In the basolateral membrane, antiporters cooperate with facilitators to release amino acids without depleting cells of valuable nutrients. With very few exceptions, individual amino acids are transported by more than one transporter, providing backup capacity for absorption in the case of mutational inactivation of a transport system.

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Transport Mechanisms of the Large Neutral Amino Acid L-Phenylalanine in the Human Intestinal Epithelial Caco-2 Cell Line

Cited by 26 publications

References 21 publications

Large neutral amino acids supplementation in phenylketonuric patients

Large neutral amino acids supplementation in phenylketonuric patients

Effect of pH on l- and d-methionine uptake across the apical membrane of Caco-2 cells

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

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