Placental amino acid transport

1995 ◽  
Vol 268 (6) ◽  
pp. C1321-C1331 ◽  
Author(s):  
A. J. Moe
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Human Placenta ◽  
Amino Acid Transport ◽  
Single Layer ◽  
Maternal Blood ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Principal Mechanism

Normal fetal growth and development depend on a continuous supply of amino acids from the mother to the fetus. The placenta is responsible for the transfer of amino acids between the two circulations. The human placenta is hemomonochorial, meaning that the maternal and fetal circulations are separated by a single layer of polarized epithelium called the syncytiotrophoblast, which is in direct contact with maternal blood. Transport proteins located in the microvillous and basal membranes of the syncytiotrophoblast are the principal mechanism for transfer from maternal blood to fetal blood. Knowledge of the function and regulation of syncytiotrophoblast amino acid transporters is of great importance in understanding the mechanism of placental transport and potentially improving fetal and newborn outcomes. The development of methods for the isolation of microvillous and basal membrane vesicles from human placenta over the past two decades has contributed greatly to this understanding. Now a primary cultured trophoblast model is available to study amino acid transport and regulation as the cells differentiate. The types of amino acid transporters and their distribution between the syncytiotrophoblast microvillous and basal membranes are somewhat unique compared with other polarized epithelia. These differences may reflect the unusual circumstance of this epithelium that is exposed to blood on both sides. The current state of knowledge as to the types of transport systems present in syncytiotrophoblast, their regulation, and the effects of maternal consumption of drugs on transport are discussed.

scholarly journals The Proposed Neurotoxin β-N-Methylamino-l-Alanine (BMAA) Is Taken up through Amino-Acid Transport Systems in the Cyanobacterium Anabaena PCC 7120

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 518
Author(s):  
Zi-Qian Wang ◽  
Suqin Wang ◽  
Ju-Yuan Zhang ◽  
Gui-Ming Lin ◽  
Nanqin Gan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Transport Pathways ◽  
Anabaena Pcc 7120 ◽  
Cyanobacterium Anabaena ◽  
Pcc 7120

Produced by cyanobacteria and some plants, BMAA is considered as an important environmental factor in the occurrence of some neurodegenerative diseases. Neither the underlying mechanism of its toxicity, nor its biosynthetic or metabolic pathway in cyanobacteria is understood. Interestingly, BMAA is found to be toxic to some cyanobacteria, making it possible to dissect the mechanism of BMAA metabolism by genetic approaches using these organisms. In this study, we used the cyanobacterium Anabaena PCC 7120 to isolate BMAA-resistant mutants. Following genomic sequencing, several mutations were mapped to two genes involved in amino acids transport, suggesting that BMAA was taken up through amino acid transporters. This conclusion was supported by the protective effect of several amino acids against BMAA toxicity. Furthermore, targeted inactivation of genes encoding different amino acid transport pathways conferred various levels of resistance to BMAA. One mutant inactivating all three major amino acid transport systems could no longer take up BMAA and gained full resistance to BMAA toxicity. Therefore, BMAA is a substrate of amino acid transporters, and cyanobacteria are interesting models for genetic analysis of BMAA transport and metabolism.

scholarly journals A new family of proteins (rBAT and 4F2hc) involved in cationic and zwitterionic amino acid transport: a tale of two proteins in search of a transport function.

1994 ◽  
Vol 196 (1) ◽  
pp. 123-137 ◽  
Author(s):  
M Palacín
Keyword(s):  
Amino Acids ◽  
Small Intestine ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Cdna Clones ◽  
Missense Mutations ◽  
Acid Transport ◽  
High Affinity

The currently identified cDNA clones of mammalian amino acid transporters can be grouped into five different families. One family is composed of the proteins rBAT and the heavy chain (hc) of the cell surface antigen 4F2. RNAs encoding these two proteins induce a system b(o,+)-like (rBAT) and a system y+L-like (4F2hc) activity in Xenopus oocytes. Surprisingly, rBAT and 4F2hc do not seem to be pore-forming proteins. This finding supports the hypothesis that rBAT and 4F2hc are subunits or modulators of the corresponding amino acid transport systems. Expression of rBAT in oocytes induces high-affinity transport of cystine, which is shared with transport of cationic and zwitterionic amino acids. The rBAT gene is expressed mainly in kidney and small intestine. The rBAT protein is localized to the microvilli of proximal straight tubules of the kidney and mucosa from the small intestine. This finding is consistent with the involvement of rBAT in a high-affinity resorption system for cystine in the proximal straight tubule of the nephron. All of these characteristics suggest that rBAT is a good candidate for a cystinuria gene. Cystinuria is an inheritable defect in high-affinity transport of cystine, shared with cationic amino acids, through epithelial cells of the renal tubule and intestinal tract. Very recently, point missense mutations have been found in the rBAT gene of cystinuria patients. The most frequent rBAT mutation, M467T (threonine substitution of methionine at residue 467) nearly abolished the amino acid transport activity elicited by rBAT in oocytes. This result offers convincing evidence that rBAT is a cystinuria gene. Biochemical, cytological and genetic approaches are now needed to delineate the mechanism of action of rBAT and 4F2hc in the transport of amino acids.

System β and System A amino acid transporters in the feline endotheliochorial placenta

2004 ◽  
Vol 287 (6) ◽  
pp. R1369-R1379 ◽  
Author(s):  
E. E. Champion ◽  
S. J. Mann ◽  
J. D. Glazier ◽  
C. J. P. Jones ◽  
J. M. Rawlings ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Placenta ◽  
Amino Acid Transport ◽  
Time Course ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Transport Mechanisms ◽  
Acid Transport ◽  
System A ◽  
Taurine Uptake

There is no knowledge of the transport mechanisms by which solutes cross the cat placenta or any other endotheliochorial placenta. Here, we investigated whether the amino acid transport systems β and A are present in the cat placenta using a placental fragment uptake technique. Data were compared with studies in the human placenta, in which the presence of these two transport systems has been well established. A time course of [3H]taurine (substrate for system β) and [14C]MeAIB (nonmetabolizable substrate for system A) uptake was determined in the term cat and human placental fragments in the presence and absence (choline substituted) of Na+, and further studies were carried out over 15 min. Taurine uptake into both cat and human placenta fragments was found to be Na+ and Cl− dependent, and Na+-dependent taurine uptake was blocked by excess β-alanine. MeAIB uptake was found to be Na+ dependent, and Na+-dependent MeAIB uptake was blocked by excess MeAIB or glycine. Western blotting and immunohistochemistry performed on cat and human placenta showed expression of TAUT and ATA2 (SNAT2), proteins associated with system β and system A activity, respectively. This study therefore provides the first evidence of the presence of amino acid transport systems β and A in the cat placenta.

Amino Acid Transport in a Water-mould: The Possible Regulatory Roles of Calcium and N6-(Δ2-isopentenyl)adenine

1975 ◽  
Vol 53 (9) ◽  
pp. 975-988 ◽  
Author(s):  
Danny P. Singh ◽  
Hérb. B. LéJohn
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Osmotic Shock ◽  
Inhibitory Effect ◽  
Transport Systems ◽  
Acid Transport ◽  
Isopentenyl Adenine ◽  
Energy Dependent ◽  
Water Mould

Transport of amino acids in the water-mould Achlya is an energy-dependent process. Based on competition kinetics and studies involving the influence of pH and temperature on the initial transport rates, it was concluded that the 20 amino acids (L-isomers) commonly found in proteins were transported by more than one, possibly nine, uptake systems. This is similar to the pattern elucidated for some bacteria but unlike those uncovered for all fungi studied to date. The nine different transport systems elucidated are: (i) methionine, (ii) cysteine, (iii) proline, (iv) serine–threonine, (v) aspartic and glutamic acids, (vi) glutamine and asparagine, (vii) glycine and alanine, (viii) histidine, lysine, and arginine, and (ix) phenylalanine–tyrosine–tryptophan and leucine–isoleucine–valine as two overlapping groups. Transport of all of these amino acids was inhibited by azide, cyanide, and its derivatives and 2,4-dinitrophenol. These agents normally interfere with metabolism at the level of the electron transport chain and oxidative phosphorylation. Osmotic shock treatment of the cells released, into the shock fluid, a glycopeptide that binds calcium as well as tryptophan but no other amino acid. The shocked cells are incapable of concentrating amino acids, but remain viable and reacquire this capacity when the glycopeptide is resynthesized.Calcium played more than a secondary role in the transport of the amino acids. When bound to the membrane-localized glycopeptide, it permits concentrative transport to take place. However, excess calcium can inhibit transport which can be overcome by chelating with citrate. Calculations show that the concentration of free citrate is most important. At low citrate concentrations (less than 1 mM) in the absence of exogenously supplied calcium, enhancement of amino acid transport occurs. At high concentrations (greater than 5 mM), citrate inhibits but this effect can be reversed by titrating with calcium. Evidently, the glycopeptide acts as a calcium sink to regulate the concentration of calcium made available to the cell for its membrane activities.N6-(Δ2-isopentenyl) adenine (a plant growth 'hormone') and analogues mimic the inhibitory effect of citrate and bind to the glycopeptide as well. Replot data for citrate and N6-(Δ2-isopentyl) adenine inhibition indicate that both agents have no more than one binding constant. These results implicate calcium, glycopeptide, and energy-dependent transport of solutes in some, as yet undefinable, way.

Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3

2005 ◽  
Vol 288 (2) ◽  
pp. C290-C303 ◽  
Author(s):  
Tiziano Verri ◽  
Cinzia Dimitri ◽  
Sonia Treglia ◽  
Fabio Storelli ◽  
Stefania De Micheli ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Line ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Residual Fraction ◽  
Acid Transport ◽  
Thyroid Cells ◽  
Cationic Amino Acid ◽  
Rat Thyroid

Information regarding cationic amino acid transport systems in thyroid is limited to Northern blot detection of y+LAT1 mRNA in the mouse. This study investigated cationic amino acid transport in PC cell line clone 3 (PC Cl3 cells), a thyroid follicular cell line derived from a normal Fisher rat retaining many features of normal differentiated follicular thyroid cells. We provide evidence that in PC Cl3 cells plasmalemmal transport of cationic amino acids is Na+ independent and occurs, besides diffusion, with the contribution of high-affinity, carrier-mediated processes. Carrier-mediated transport is via y+, y+L, and b0,+ systems, as assessed by l-arginine uptake and kinetics, inhibition of l-arginine transport by N-ethylmaleimide and neutral amino acids, and l-cystine transport studies. y+L and y+ systems account for the highest transport rate (with y+L > y+) and b0,+ for a residual fraction of the transport. Uptake data correlate to expression of the genes encoding for CAT-1, CAT-2B, 4F2hc, y+LAT1, y+LAT2, rBAT, and b0,+AT, an expression profile that is also shown by the rat thyroid gland. In PC Cl3 cells cationic amino acid uptake is under TSH and/or cAMP control (with transport increasing with increasing TSH concentration), and upregulation of CAT-1, CAT-2B, 4F2hc/y+LAT1, and rBAT/b0,+AT occurs at the mRNA level under TSH stimulation. Our results provide the first description of an expression pattern of cationic amino acid transport systems in thyroid cells. Furthermore, we provide evidence that extracellular l-arginine is a crucial requirement for normal PC Cl3 cell growth and that long-term l-arginine deprivation negatively influences CAT-2B expression, as it correlates to reduction of CAT-2B mRNA levels.

Amino-acid-dependent modulation of amino acid transport in Xenopus laevis oocytes.

1996 ◽  
Vol 199 (4) ◽  
pp. 923-931 ◽  
Author(s):  
P M Taylor ◽  
S Kaur ◽  
B Mackenzie ◽  
G J Peter
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Xenopus Laevis ◽  
Amino Acid Transport ◽  
Acid Mixture ◽  
Xenopus Laevis Oocytes ◽  
Amino Acid Transporters ◽  
Amino Acid Supplementation ◽  
Acid Transport ◽  
Acid Supplementation

We have measured rates of uptake of arginine, glutamine, glutamate, serine, phenylalanine and glycine in Xenopus laevis oocytes cultured for periods of up to 24h in saline in the presence or absence of a mixture of 20 amino acids at concentrations approximating those in Xenopus plasma. Amino acid supplementation increased the total intracellular amino acid concentration from 8.2 to 18.4 nmol per oocyte. Specific Na(+)-dependent amino acid transporters (systems B0,+, Xag-) exhibit 'adaptive regulation' (up-regulation during amino acid deprivation and down-regulation during amino acid supplementation). Na(+)-independent transporters of glutamate, glutamine and glycine (including system asc) display an opposite modulation in activity, which may help to combat amino-acid-induced oxidative stress by increasing the supply of glutathione precursors. Single amino acids at physiological plasma concentrations (0.47 mmol l-1 L-alanine, 0.08 mmol l-1 L-glutamate) mimicked at least some effects of the amino acid mixture. The mechanisms of transport modulation do not appear to include trans-amino acid or membrane potential effects and, in the case of Na(+)-independent transport, are independent of protein or mRNA synthesis. Furthermore, activation of protein kinase C by phorbol 12-myristate 13-acetate did not significantly affect endogenous glutamine and glutamate transport. The Xenopus oocyte appears to possess endogenous signalling mechanisms for selectively modulating the activity of amino acid transport proteins expressed in its surface membranes, a factor for consideration when using oocytes as an expression system for structure-function studies of cloned amino acid transporters.

Amino acid transport systems in intestinal brush-border membranes from lepidopteran larvae

1989 ◽  
Vol 257 (3) ◽  
pp. R494-R500 ◽  
Author(s):  
B. Giordana ◽  
V. F. Sacchi ◽  
P. Parenti ◽  
G. M. Hanozet
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brush Border ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Acid Transport ◽  
Specific System ◽  
Neutral Amino Acids ◽  
Intestinal Brush Border ◽  
Lepidopteran Larvae

Experiments with intestinal brush-border membrane vesicles from lepidopteran larvae disclosed the occurrence of unique cotransporter proteins that use K+ as the driver cation for the transmembrane transfer of amino acids across the luminal border of midgut enterocytes. Six apical membrane amino acid transport systems have been identified. These systems are 1) a neutral amino acid transporter with a broad spectrum of interactions with most neutral amino acids, which is highly concentrative, strongly K+- and electrical potential-dependent, poorly stereospecific, and recognizes histidine, but not proline, glycine, or alpha-(methylamino)isobutyric acid (MeAIB); 2) a specific system for L-proline; 3) a specific system for glycine with a higher affinity for Na+ than for K+; 4) a specific system for L-lysine, which is dependent on membrane potential, is highly sensitive to external K+, and does not interact with L-arginine or neutral amino acids; 5) a specific K+-dependent process for glutamic acid, which does not recognize aspartic acid; and last, 6) an apparently unique K+- driven mechanism for D-alanine, which is potential-dependent and strongly stereospecific.

Heteromeric amino acid transporters: biochemistry, genetics, and physiology

2001 ◽  
Vol 281 (6) ◽  
pp. F995-F1018 ◽  
Author(s):  
Josep Chillarón ◽  
Ramón Roca ◽  
Alfonso Valencia ◽  
Antonio Zorzano ◽  
Manuel Palacín
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Human Genetics ◽  
Disulfide Bridge ◽  
Transport Systems ◽  
Cell Physiology ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Membrane Glycoproteins ◽  
Cell Functions

The heteromeric amino acid transporters (HATs) are composed of two polypeptides: a heavy subunit (HSHAT) and a light subunit (LSHAT) linked by a disulfide bridge. HSHATs are N-glycosylated type II membrane glycoproteins, whereas LSHATs are nonglycosylated polytopic membrane proteins. The HSHATs have been known since 1992, and the LSHATs have been described in the last three years. HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y+L isoforms, asc, x[Formula: see text], and b0,+). Members of the HAT family are the molecular bases of inherited primary aminoacidurias cystinuria and lysinuric protein intolerance. In addition to the role in amino acid transport, one HSHAT [the heavy subunit of the cell-surface antigen 4F2 (also named CD98)] is involved in other cell functions that might be related to integrin activation. This review covers the biochemistry, human genetics, and cell physiology of HATs, including the multifunctional character of CD98.

AMINO ACID TRANSPORT IN BRAIN CORTEX SLICES: II. COMPETITION BETWEEN AMINO ACIDS

1962 ◽  
Vol 40 (11) ◽  
pp. 1591-1602 ◽  
Author(s):  
P. N. Abadom ◽  
P. G. Scholefield
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Brain ◽  
Amino Acid Transport ◽  
Brain Cortex ◽  
Transport Systems ◽  
Acid Transport ◽  
Inhibitory Effects ◽  
Brain Cortex Slices ◽  
Cortex Slices

Evidence is presented which indicates that several amino acid transport systems are present in rat brain cortex slices, each with its own specificity with regard to substrate and with regard to amino acids which produce inhibitory effects. The nature of these inhibitory effects may be either direct (competition for a limiting number of sites) or indirect (as they are when glutamate or aspartate cause a decrease in the ATP content).Comparison of the specificities of the glycine transport systems present in rat brain cortex slices and in Ehrlich ascites carcinoma cells indicates that these two systems have little in common and the relation of this finding to the structural requirements necessary for chemotherapeutic activity is discussed.

In vivo muscle amino acid transport involves two distinct processes

2004 ◽  
Vol 287 (1) ◽  
pp. E136-E141 ◽  
Author(s):  
Sharon Miller ◽  
David Chinkes ◽  
David A. MacLean ◽  
Dennis Gore ◽  
Robert R. Wolfe
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Interstitial Fluid ◽  
Muscle Blood Flow ◽  
Amino Acid Uptake ◽  
Transport Systems ◽  
Acid Uptake ◽  
Acid Transport ◽  
Rate Limiting

We have tested the hypothesis that transit through the interstitial fluid, rather than across cell membranes, is rate limiting for amino acid uptake from blood into muscle in human subjects. To quantify muscle transmembrane transport of naturally occurring amino acids, we developed a novel 4-pool model that distinguishes between the interstitial and intracellular fluid compartments. Transport kinetics of phenylalanine, leucine, lysine, and alanine were quantified using tracers labeled with stable isotopes. The results indicate that interstitial fluid is a functional compartment insofar as amino acid kinetics are concerned. In the case of leucine and alanine, transit between blood and interstitial fluid was potentially rate limiting for muscle amino acid uptake and release in the postabsorptive state. For example, in the case of leucine, the rate of transport between blood and interstitial fluid compared with the corresponding rate between interstitial fluid and muscle was 247 ± 36 vs. 610 ± 95 nmol·min−1·100 ml leg−1, respectively ( P < 0.05). Our results are consistent with the process of diffusion governing transit from blood to interstitial fluid without selectivity, and of specific amino acid transport systems with varying degrees of efficiency governing transit from interstitial fluid to muscle. These results imply that changes in factors that affect the transit of amino acids from blood through interstitial fluid, such as muscle blood flow or edema, could play a major role in controlling the rate of muscle amino acid uptake.

Sign in / Sign up

Export Citation Format

Share Document