Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta

2001 ◽  
Vol 356 (3) ◽  
pp. 719-725 ◽  
Author(s):  
James W. A. RITCHIE ◽  
Peter M. TAYLOR

The feto-placental unit relies on a maternal supply of indispensable amino acids and iodothyronines for early development and normal growth. We examined the role of the System L transporter in placental uptake of these substances, using the human placental choriocarcinoma cell line BeWo as a model experimental system. BeWo cells express both heavy (4F2hc) and light (LAT1, LAT2) chains of the System L holotransporter. Saturable transport of both l-[3H]tryptophan and [125I]tri-iodo-l-thyronine in BeWo cells includes components sensitive to inhibition by the System-L-specific substrate 2-endoamino-bicycloheptane-2-carboxylic acid; kinetic properties of these components indicate that the 4F2hc-LAT1 transporter isoform is likely to predominate for the carriage of both substances at physiologically relevant concentrations. Both 4F2hc and LAT1 proteins are also expressed in human placental membranes and LAT1 at least is localized largely to the syncytiotrophoblast layer of the term human placenta. The 4F2hc-LAT1 transporter might therefore serve a vital role in supplying the developing fetus and the placenta with both thyroid hormones and indispensable amino acids from the maternal circulation.

1992 ◽  
Vol 281 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Y Zhou ◽  
M Samson ◽  
J Francon ◽  
J P Blondeau

The kinetic properties of transport system T, which is specific for uptake of aromatic amino acids, were studied in rat erythrocytes in the presence of leucine in order to block the neutral amino acid transport system L. Since the triiodothyronine (T3) transport system and system T are closely related, the trans effect of T3 and tryptophan on [3H]tryptophan transport and the trans effects of aromatic amino acids on [125I]T3 transport were studied. Equilibrium-exchange, zero-trans and infinite-trans studies of [3H]tryptophan transport indicated that system T in rat erythrocytes is a simple carrier with exchanging properties resulting in trans-acceleration of influx and trans-inhibition of efflux when tryptophan was present at the trans side of the membrane. In erythrocytes preloaded with unlabelled tryptophan, countertransport resulted in a 7-fold accumulation of labelled substrate inside the cells. T3 on the trans side of the membrane inhibited both influx and efflux of tryptophan, with Ki values similar to the Km values of the T3 transport system. Extracellular tryptophan trans-inhibited [125I]T3 efflux in a manner similar to [3H]tryptophan efflux. Preloading erythrocytes with tryptophan resulted in trans-acceleration of T3 uptake and a transient 5-fold accumulation of free T3 into erythrocytes. Phenylalanine and tyrosine (but not the D-isomer of tryptophan or non-aromatic amino acids) also produced trans-acceleration for T3 uptake and T3 countertransport. These results are compatible with a kinetic model assuming a common simple carrier of T3 and tryptophan transport and point to a countertransport pathway driving the uphill uptake of T3 by hetero-exchange with intracellular aromatic amino acids.


2022 ◽  
Vol 8 ◽  
Author(s):  
Nick W. Smith ◽  
Andrew J. Fletcher ◽  
Jeremy P. Hill ◽  
Warren C. McNabb

Nutrient-rich foods play a major role in countering the challenges of nourishing an increasing global population. Milk is a source of high-quality protein and bioavailable amino acids, several vitamins, and minerals such as calcium. We used the DELTA Model, which calculates the delivery of nutrition from global food production scenarios, to examine the role of milk in global nutrition. Of the 29 nutrients considered by the model, milk contributes to the global availability of 28. Milk is the main contributing food item for calcium (49% of global nutrient availability), Vitamin B2 (24%), lysine (18%), and dietary fat (15%), and contributes more than 10% of global nutrient availability for a further five indispensable amino acids, protein, vitamins A, B5, and B12, phosphorous, and potassium. Despite these high contributions to individual nutrients, milk is responsible for only 7% of food energy availability, indicating a valuable contribution to global nutrition without necessitating high concomitant energy intakes. Among the 98 food items considered by the model, milk ranks in the top five contributors to 23 of the 29 nutrients modeled. This quantification of the importance of milk to global nutrition in the current global food system demonstrates the need for the high valuation of this food when considering future changes to the system.


1986 ◽  
Vol 251 (1) ◽  
pp. F81-F86 ◽  
Author(s):  
B. J. Maroni ◽  
G. Karapanos ◽  
W. E. Mitch

Neutral amino acids are transported by systems A, ASC, and L. In the previous companion study we demonstrated that 2-(methylamino) isobutyrate (MeAIB) is a specific substrate for system A in muscle and that stimulation of system A by physiological concentrations of insulin is preserved in acute uremia (ARF). Insulin-stimulated uptake of the nonspecific probes cycloleucine and alpha-aminoisobutyrate (AIB) is reportedly blunted by uremia; the cause of this and whether transport by systems ASC and L is defective are unknown. In this study we examined these questions using incubated epitrochlearis muscles from normal fed, ARF, and sham-operated control (SO) rats. System ASC was studied by measuring AIB and cycloleucine uptake in the presence of inhibitors of systems A and L, MeAIB and 2-amino-2-norbornane carboxylic acid (BCH), respectively. System L was defined as sodium-independent uptake suppressible by BCH. Excess MeAIB completely inhibited insulin-stimulated AIB and cycloleucine uptake, indicating that system A is the only insulin-responsive neutral amino acid carrier in muscle. In ARF and SO mucles both AIB and cycloleucine uptake were indistinguishable in the absence or presence of insulin. Moreover, ARF caused no detectable abnormality in transport by systems ASC and L.


1981 ◽  
Vol 31 (1) ◽  
pp. 189-193 ◽  
Author(s):  
Mohamed A. Ashy ◽  
Abd El-Galil ◽  
M. Khalil ◽  
Abou-Zeid A. Abou-Zeid
Keyword(s):  

2016 ◽  
pp. 43-47
Author(s):  
O.V. Basystyi ◽  

The data of domestic and foreign literature on etiology, pathogenesis and intrauterine growth retardation diagnosis are presented in the paper. It highlights pathogenetic role of nitric oxide deficiency in case of obstetric complications and intrauterine growth retardation. Key words: intrauterine growth retardation (IUGR), system L-arginin–NO, obstetric complications.


2020 ◽  
Vol 27 (9) ◽  
pp. 923-929
Author(s):  
Gaurav Pandey ◽  
Prem Prakash Das ◽  
Vibin Ramakrishnan

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.


2019 ◽  
Vol 20 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Yi Wu ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S42-S42
Author(s):  
Kohei Sugihara ◽  
Nobuhiko Kamada

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.


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