Transport systems, amino acids

Transcription factors, 50, 399,444,592 gene activaticm, 588-590 Transferrin, 741-742, 755, 756 Transferrin infCeptOr, 50, 755 Transfer RNA, set tRNA Transketolase, 604,607 Translation, 36-37,38 0, 748,826-827 Transport systems, amino acids, 89 TRH (thyrotiiopin-releasing barmone), 735 Tricarboxylic acid cycle, 228 TrigJyfieridEs... 

Interesting as it is, the study of transporters for amino acids and other nitrogenous nutrients in Saccharomyces cerevisiae is a tricky field. Many difficulties must be circumvented to avoid trivial errors. These practical problems are linked with several features of eukaryotic uptake systems, the first being the multiplicity of permeases which transport a given substrate. In relation to this, a major point is to make certain that one is not studying more than one uptake system at a time, and this can hardly be done without genetics. Once individual uptake systems have been identified and separated with the help of genetics, a second difficulty arises, which... 

Transport of amino acids across a chloroform liquid membrane with these carriers also revealed a high specificity (Scheme 2). For efficient transport, an aromatic side chain must be present and the distance between the aryl and ammonium functions is optimal in the P-aryl systems. Neither oe-phenyl-glycine 42 nor y-phenyl-butyrine 43 are transported to significant extents 25a>. These results are shown in Table 2. The selectivity with 13 contrasts sharply for that observed with typical detergents wherein side chain hydrophobicity determines the relative transport rates. 

Amino acids and some small peptides are absorbed into the enterocytes in the jejnnnm. The transport of amino acids from the lumen into the ceU is an active process, coupled to the transport of Na ions down a concentration gradient. There are at least six carrier systems with different amino acid specificities neutral amino acids (i.e. those with no net charge, e.g. branched-chain amino acids) neutral plus basic amino acids imino acids (proline, hydroxyproline) and glycine basic amino acids (e.g. arginine and lysine) P-amino acids and taurine acidic amino acids (glutamic and aspartic acids). 

The transport of amino acids at the BBB differs depending on their chemical class and the dual function of some amino acids as nutrients and neurotransmitters. Essential large neutral amino acids are shuttled into the brain by facilitated transport via the large neutral amino acid transporter (LAT) system [29] and display rapid equilibration between plasma and brain concentrations on a minute time scale. The LAT-system at the BBB shows a much lower Km for its substrates compared to the analogous L-system of peripheral tissues and its mRNA is highly expressed in brain endothelial cells (100-fold abundance compared to other tissues). Cationic amino acids are taken up into the brain by a different facilitative transporter, designated as the y system, which is present on the luminal and abluminal endothelial membrane. In contrast, active Na -dependent transporters for small neutral amino acids (A-system ASC-system) and cationic amino acids (B° system), appear to be confined to the abluminal surface and may be involved in removal of amino acids from brain extracellular fluid [30]. Carrier-mediated BBB transport includes monocarboxylic acids (pyruvate), amines (choline), nucleosides (adenosine), purine bases (adenine), panthotenate, thiamine, and thyroid hormones (T3), with a representative substrate given in parentheses [31]. 

Fluoro amino acids have been incorporated into peptides, in order to ease the transport or reduce the systemic toxicity. Thus, trifluoroalanine, a powerful inhibitor of alanine racemase, is an essential enzyme for the biosynthesis of the cell wall of bacteria. It has a low antibiotic activity because of its very poor transport. In order to facilitate this transport, the amino acid has been incorporated into a peptide. This delivery allows a reduction of the doses, and thus the toxicity of the treatment is lowered.3-FIuorophenylaIanine (3-F-Phe) is a substrate of phenylalanine hydroxylase, which transforms it into 3-F-Tyr. 3-F-Tyr has a high toxicity for animals, due to its ultimate metabolization into fluorocitrate, a powerful inhibitor of the Krebs cycle (cf. Chapter 7). 3-F-Phe has a low toxicicity toward fungus cells, but when delivered as a tripeptide 3-F-Phe becomes an efficient inhibitor of the growth of Candida albicans. This tripeptide goes into the cell by means of the active transport system of peptides, where the peptidases set free the 3-F-Phe. ... 

The most efficient rectal absorption enhancers, which have been studied, include surfactants, bile acids, sodium salicylate (NaSA), medium-chain glycerides (MCG), NaCIO, enamine derivatives, EDTA, and others [45 17]. Transport from the rectal epithelium primarily involves two routes, i.e., the paracellular route and the transcellular route. The paracellular transport mechanism implies that drugs diffuse through a space between epithelial cells. On the other hand, an uptake mechanism which depends on lipophilicity involves a typical transcellular transport route, and active transport for amino acids, carrier-mediated transport for (3-lactam antibiotics and dipeptides, and endocytosis are also involved in the transcellular transport system, but these transporters are unlikely to express in rectum (Figure 8.7). Table 8.3 summarizes the typical absorption enhancers in rectal routes. 

Lin, G., McCormick, J.I., Johnstone, R.M. (1994). Differentiation of twoclasses of A system amino acid transporters. Arch. Biochem. Biophys. 312, 308-315. 

Although the tegument contains specific systems for molecular and ion transport - especially amino acids, hexose sugars, vitamins, purines, pyrimidines, nucleotides, and lipids - it probably also serves a number of other vital functions (647) (a) it is a major site of catalytic activity and... 

Six human sugar transporters with different tissue distributions, substrate kinetics, and specificities have been identified. A number of facilitated amino acid transporters have also been identified in mammalian cells. System L, which transports neutral amino acids, such as leucine and phenylalanine, is probably the best known of these. 

Bomer, V., Fei, Y.J., Hartrodt, B., Ganapathy, V., Leibach, F.H., Neubert, K. and Brandsch, M. (1998) Transport of amino acid aryl amides by the intestinal H + /peptide cotransport system, PEPT1. European Journal of Biochemistry, 255 (3), 698-702. 

Intracellular metabolism of amino acids requires their transport across the cell membrane. Transport of L-amino acids occurs against a concentration gradient and is an active process usually coupled to Na -dependent carrier systems as for transport of glucose across the intestinal mucosa (Chapter 12). At least five transport systems for amino acids (with overlapping specificities) have been identified in kidney and intestine. They transport neutral amino acids, acidic amino acids, basic amino acids, ornithine and cystine, and glycine and proline, respectively. Within a given carrier system, amino acids may compete for transport (e.g., phenylalanine with tryptophan). Na+-independent transport carriers for neutral and lipophilic amino acids have also been described, d-Amino acids are transported by simple diffusion favored by a concentration gradient. 

The rising need for new separation processes for the biotechnology industry and the increasing attention towards development of new industrial eruyme processes demonstrate a potential for the use of liquid membranes (LMs). This technique is particularly appropriate for multiple enzyme / cofactor systems since any number of enzymes as well as other molecules can be coencapsulated. This paper focuses on the application of LMs for enzyme encapsulation. The formulation and properties of LMs are first introduced for those unfamiliar with the technique. Special attention is paid to carrier-facilitated transport of amino acids in LMs, since this is a central feature involved in the operation of many LM encapsulated enzyme bioreactor systems. Current work in this laboratory with a tyrosinase/ ascorbate system for isolation of reactive intermediate oxidation products related to L-DOPA is discussed. A brief review of previous LM enzyme systems and reactor configurations is included for reference. 

It has been shown that carrier-facilitated transport of amino acid ions plays a central role of development of LM enzyme systems. Better anion carriers and new cation carriers are needed to exploit enzymatic processes where amino acids (or derivatives) and their products must transport readily through the LM. Facile transport with little or no enzyme deactivation is required. Design of new carriers tailored specifically for LM processes will help pave the way for the industrial development of liquid membrane enzyme reactors. 

Transport of amino acids into cells is mediated by specific membrane-bound transport proteins, several of which have been identified in mammalian cells. They differ in their specificity for the types of amino acids transported and in whether the transport process is linked to the movement of Na+ across the plasma membrane. (Recall that the gradient created by the active transport of Na+ can move molecules across membrane. Na+-dependent amino acid transport is similar to that observed in the glucose transport process illustrated in Figure 11.28.) For example, several Na+-dependent transport systems have been identified within the lumenal plasma membrane of enterocytes. Na+-independent transport systems are responsible for transporting amino acids across the portion of enterocyte plasma membrane in contact with blood vessels. The y-glutamyl cycle (Section 14.3) is believed to assist in transporting some amino acids into specific tissues (i.e., brain, intestine, and kidney). 

Amino acid transport is equally poorly understood in gastrointestinal nematodes. It has been difficult to demonstrate significant transport of amino acids across the gut. Histochemical and enzymological data demonstrate that y-glutamyl transpeptidase is present in the cuticle-hypodermis of A. suum in considerably greater abundance than in the intestinal epithelium (124). This enzyme is part of an amino acid transport system found in many organisms. 

A large number of overlapping transport systems exist for amino acids in cells. Some systems contain facilitative transporters, whereas others express sodium-linked tranporters, which allow the active transport of amino acids into cells. Defects in amino acid transport can lead to disease. 

At least six different Na -dependent amino acid carriers are located in the apical brush border membrane of the epithelial cells. These carriers have an overlapping specificity for different amino acids. One carrier preferentially transports neutral amino acids, another transports proline and hydroxyproline, a third preferentially transports acidic amino acids, and a fourth ffansports basic amino acids (lysine, arginine, the urea cycle intermediate ornithine) and cystine (two cysteine residues linked by a disulfide bond). In addition to these Na -dependent carriers, some amino acids are transported across the luminal membrane by facilitated tiansport carriers. Most amino acids are transported by more than one tiansport system. 

Large neutral amino acids (LNAA, such as phenylalanine, leucine, tyrosine, isoleucine, valine, tryptophan, methionine, and histidine) rapidly enter the CSF via a single amino acid transporter. (L-[leucine preferring]-system amino acid transporter). Many of these compounds are essential in the diet and must be imported for protein synthesis or as precursors of neurotransmitters. Because a single transporter is involved, these amino acids compete with each other for transport into the brain. 

Transport of amino acids across the apical membrane is not only via sodium-dependent symporters but also due to the proton-motive force and the gradient of other amino acids providing to absorb amino acids from the lumen efficiently. In the basolateral membrane, antiporters work together with facilitators to release amino acids without depleting cells of valuable nutrients. Individual amino acids are mostly transported by more than one transporter, affording a backup capacity for the absorption during the mutational inactivation of a transport system (Broer, 2008). 

UV irradiated for 20 min. followed by being visible light irradiated for 5 min, a significant transfer of phenylalanine from the liposome to the outer solvent took place. No transport of amino acid was observed in the dark or in the absence of 1. The system suffers from several drawbacks, including the question of the integrity of the membrane under the conditions of the experiment and the photochemical instability of the photospiran 1. However, in spite of such limitations. Sunamoto s work established for the first time the simple concept of charge complementarity for recognition and transport of the zwitterionic form of amino acids, as schematically depicted in Eq. 2 (see below). 

Chishty M, Reichel A, Begley DJ, Abbott NJ. Glial induction of blood-brain barrier-like L-system amino acid transport in the EC304 cell line. Glia 2002 39 99-104. 

Applications for molecular dynamics in microfluidic systems include protein folding in solution, transport of amino acids in ion channels, and locally driven electroosmotic flows with rigid particles. However, these applications do not involve the bulk motion of a fluid and are extremely small, specialized systems. In general. 

Only limited information is available regarding the transport of amino acids across cell membranes in plants 243, 263). Active carrier-mediated transport of amino acids into plant cells has been demonstrated in a number of different systems. In some cases competition experiments have indicated a single transport system for all amino acids, but in other cases there is evidence to indicate the existence of different transport systems for different groups of amino acids. 

The active transport of amino acids and their accumulation in vacuoles has been demonstrated with carrot slices 16, 17, 33). Active transport of amino acids has been shown for leaf strips of barley (2, 273, 308) and for leaf slices of barley 200). In the latter investigation competition experiments indicated a single carrier system for all amino acids. However, experiments on the uptake of amino acids into barley roots indicated different transport systems for lysine -i- arginine, proline, and methionine, respectively 310). 

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