Transport antiport

The interplay of H, K, Na", and the transmembrane potential and their effect on membrane transport is a complex phenomenon. Which factors are the independent variables in a transport process and which are the dependent variables is difficult to determine. However, it is well-established that transport of many amino acids, sugars, and other carbon and nitrogen sources requires the co-transport (symport) of an ion along with it and probably the reverse transport (antiport) of a similarly charged ion. 

The gradients of H, Na, and other cations and anions established by ATPases and other energy sources can be used for secondary active transport of various substrates. The best-understood systems use Na or gradients to transport amino acids and sugars in certain cells. Many of these systems operate as symports, with the ion and the transported amino acid or sugar moving in the same direction (that is, into the cell). In antiport processes, the ion and the other transported species move in opposite directions. (For example, the anion transporter of erythrocytes is an antiport.) Proton symport proteins are used by E. coU and other bacteria to accumulate lactose, arabinose, ribose, and a variety of amino acids. E. coli also possesses Na -symport systems for melibiose as well as for glutamate and other amino acids. 

The site level at which [Ca2+]i regulates NCX activity (CBD) is different from the one required for Ca2+ transport. Submicromolar concentrations (0.1-0.3 pM) of intracellular Ca2+ are needed to activate the antiporter through these Ca2+ binding site. The location of such regulatory site has been identified in the 134-amino acid-length region, situated in the center of the intracellular f loop [2], (Table 1)... 

Sialin was first identified as the product of the gene defective in sialidosis, a lysosomal storage disorder. The transporter mediates the movement of sialic acid out of lysosomes by coupling to the proton electrochemical gradient across the lysosomal membrane. Unlike the vesicular neurotransmitter transporters which are antiporters, sialin is a sympoiter with sialic acid and protons both moving out of the lysosome. 

Figure 12-11. Combination of phosphate transporter ( ) with the adenine nucleotide transporter ((2)) in ATP synthesis. The H+ZP, symport shown is equivalent to the P /OH antiport shown in Figure 12-10. Four protons are taken into the mitochondrion for each ATP exported. However, one less proton would be taken in when ATP is used inside the mitochondrion.

Transport systems can be described in a functional sense according to the number of molecules moved and the direction of movement (Figure 41-10) or according to whether movement is toward or away from equilibrium. A uniport system moves one type of molecule bidirectionally. In cotransport systems, the transfer of one solute depends upon the stoichiometric simultaneous or sequential transfer of another solute. A symport moves these solutes in the same direction. Examples are the proton-sugar transporter in bacteria and the Na+ -sugar transporters (for glucose and certain other sugars) and Na -amino acid transporters in mammalian cells. Antiport systems move two molecules in opposite directions (eg, Na in and Ca out). 

Ionization may be used to counteract disregulation of pH levels (which is maintained through the concerted action of Na /H antiporters, CL/HCO3" exchangers, and other channels and/or transporters that exist within the plasma membrane of eucaryotic cells [32,100,101]). Indeed, it has been shown that iono-phores (such as nigericin [102]) can lower the intracellular pH, while weak acids (such as propionic acid) can promote acidification. Likewise, nonsteroidal anti-... 

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

Takanaga, H., et al. Nicotinic acid transport mediated by pH-dependent anion antiporter and proton cotransporter in rabbit intestinal brush-border membrane. J. Pharm. Pharmacol. 1996, 48, 1073-1077. 

Krupka, R. M., Uncoupled active transport mechanisms accounting for low selectivity in multidrug carriers P-glycoprotein and SMR antiporters,... 

ATP-dependent Ca2+ pumps and Na+,Ca2+ antiporters act in concert to maintain a low concentration of free cytosolic Ca2+ 79 The uniquely high resolution structural data available for the SERCAla Ca2+ pump illuminates the structure of all P-type transporters 81 P-type copper transporters are important for neural function 82... 

The recovery of neurotransmitters from synaptic clefts and their storage in cytoplasmic vesicles is accomplished by the tandem actions of the secondary transporters in plasma and vesicular membranes 84 Packaging neurotransmitters into presynaptic vesicles is mediated by proton-coupled antiporters 86... 

Glutamate transporters in brain are coded by five different but closely related genes, SLC1A1-4 and SLC1A6. There are several trivial names for each of the corresponding proteins. The transporters can all symport one Glu, with three Na+ and one H+, and antiport one K+ within each cycle, but they differ in their cellular expression. 

Na+,H+ antiporters (NHE) occur in synaptosomes, glia and neuroblastoma cells [60] (Fig. 5-8B). They are relatively inactive at neutral pH but with a decrease in intracellular pH they produce an efflux of protons at the expense of the Na+ gradient. The NHE transport stoichiometry is 1 1. Activation by an internal pH decrement apparently results from protonation of a cytoplasmic site, which allosterically increases the affinity of the proton ionophoric site. In some cells, the NHE is under additional control by receptor mechanisms. Several growth factors and hormones produce transient cytoplasmic alkalinization, probably by mediating a protein kinase... 

Eiden, L. E., Schafer, M. K.-H., Weihe, E. and Schiitz, B. The vesicular amine transporter family (SLC18) amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine. Eur. J. Physiol. 447 636-640, 2004. 

KAMMERER, B, FISHCER, K., HILPERT, B., SCHUBERT, S, GUTENSOHN, M., WEBER, A., FLUGGE, U.-I., Molecular characterization of a carbon transporter in plastids from heterotrophic tissues the glucose 6-phosphate phosphate antiporter, Plant Cell, 1998,10, 105-117. 

Figure 1. Solute transfer across an idealised eukaryote epithelium. The solute must move from the bulk solution (e.g. the external environment, or a body fluid) into an unstirred layer comprising water/mucus secretions, prior to binding to membrane-spanning carrier proteins (and the glycocalyx) which enable solute import. Solutes may then move across the cell by diffusion, or via specific cytosolic carriers, prior to export from the cell. Thus the overall process involves 1. Adsorption 2. Import 3. Solute transfer 4. Export. Some electrolytes may move between the cells (paracellular) by diffusion. The driving force for transport is often an energy-requiring pump (primary transport) located on the basolateral or serosal membrane (blood side), such as an ATPase. Outward electrochemical gradients for other solutes (X+) may drive import of the required solute (M+, metal ion) at the mucosal membrane by an antiporter (AP). Alternatively, the movement of X+ down its electrochemical gradient could enable M+ transport in the same direction across the membrane on a symporter (SP). A, diffusive anion such as chloride. Kl-6 refers to the equilibrium constants for each step in the metal transfer process, Kn indicates that there may be more than one intracellular compartment involved in storage. See the text for details...

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