Cotransporter

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Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport (secondary active transport) and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters. [1]

Contents

Basic difference between the cotransporters known as antiporters and symporters, and the uniporter transporter. Cotransporters.png
Basic difference between the cotransporters known as antiporters and symporters, and the uniporter transporter.

Background

Cotransporters are capable of moving solutes either up or down gradients at rates of 1000 to 100000 molecules per second. They may act as channels or transporters, depending on conditions under which they are assayed. The movement occurs by binding to two molecules or ions at a time and using the gradient of one solute's concentration to force the other molecule or ion against its gradient. Some studies show that cotransporters can function as ion channels, contradicting the classical models. For instance the wheat HKT1 transporter shows two modes of transport by the same protein. [2]

Cotransporters can be classified as antiporters and symporters. Both use electric potential and/or chemical gradients to move protons and ions against their concentration gradient. In plants the proton is considered a secondary substance and high proton concentration in the apoplast powers the inward movement of certain ions by symporters. A Proton gradient moves the ions into the vacuole by proton-sodium antiporter or the proton-calcium antiporter. In plants, sucrose transport is distributed throughout the plant by the proton-pump where the pump, as discussed above, creates a gradient of protons so that there are many more on one side of the membrane than the other. As the protons diffuse back across the membrane, the free energy liberated by this diffusion is used to co-transport sucrose. In mammals, glucose is transported through sodium dependent glucose transporters, which use energy in this process. Here, since both glucose and sodium are transported in the same direction across the membrane, they would be classified as symporters. The glucose transporter system was first hypothesized by Dr. Robert K. Crane in 1960, this is discussed later in the article. [2] [3]

History

Dr Robert K. Crane and his sketch for coupled cotransport Dr Robert K. Crane and his sketch for coupled cotransport.png
Dr Robert K. Crane and his sketch for coupled cotransport

Dr. Robert K. Crane, a Harvard graduate, had been working in the field of carbohydrate biochemistry for quite some time. His experience in the areas of glucose-6-phosphate biochemistry, carbon dioxide fixation, hexokinase and phosphate studies led him to hypothesize cotransport of glucose along with sodium through the intestine. Pictured right is of Dr. Crane and his drawing of the cotransporter system he proposed in 1960, at the international meet on membrane transport and metabolism. His studies were confirmed by other groups and are now used as the classical model to understand cotransporters. [4]

Mechanism

Antiporters and symporters both transport two or more different types of molecules at the same time in a coupled movement. An energetically unfavored movement of one molecule is combined with an energetically favorable movement of another molecule(s) or ion(s) to provide the power needed for transport. This type of transport is known as secondary active transport and is powered by the energy derived from the concentration gradient of the ions/molecules across the membrane the cotransporter protein is integrated within. [1]

Cotransporters undergo a cycle of conformational changes by linking the movement of an ion with its concentration gradient (downhill movement) to the movement of a cotransported solute against its concentration gradient (uphill movement). [5] In one conformation the protein will have the binding site (or sites in the case of symporters) exposed to one side of the membrane. Upon binding of both the molecule which is to be transported uphill and the molecule to be transported downhill a conformational change will occur. This conformational change will expose the bound substrates to the opposite side of the membrane, where the substrates will disassociate. Both the molecule and the cation must be bound in order for the conformational change to occur. This mechanism was first introduced by Oleg Jardetzky in 1966. [6] This cycle of conformational changes only transports one substrate ion at a time, which results in a fairly slow transport rate (100 to 104 ions or molecules per second) when compared to other transport proteins like ion channels. [1] The rate at which this cycle of conformational changes occurs is called the turnover rate (TOR) and is expressed as the average number of complete cycles per second performed by a single cotransporter molecule. [5]

Types

antiporter Antiporter alone.png
antiporter
symporter Symporter alone.png
symporter

Antiporters

Antiporters use the mechanism of cotransport (coupling the movement of one ion or molecule down its concentration gradient with the transport of another ion or molecule up its concentration gradient), to move the ions and molecule in opposite directions. [1] In this situation one of the ions will move from the exoplasmic space into the cytoplasmic space while the other ion will move from the cytoplasmic space into the exoplasmic space. An example of an antiporter is the sodium-calcium exchanger. The sodium-calcium exchanger functions to remove excess calcium from the cytoplasmic space into the exoplasmic space against its concentration gradient by coupling its transport with the transport of sodium from the exoplasmic space down its concentration gradient (established by the active transport of sodium out of the cell by the sodium-potassium pump) into the cytoplasmic space. The sodium-calcium exchanger exchanges 3 sodium ions for 1 calcium ion and represents a cation antiporter. [7]

Cells also contain anion antiporters such as the Band 3 (or AE1) anion transport protein. This cotransporter is an important integral protein in mammalian erythrocytes and moves chloride ion and bicarbonate ion in a one-to-one ratio across the plasma membrane based only on the concentration gradient of the two ions. The AE1 antiporter is essential in the removal of carbon dioxide waste that is converted to bicarbonate inside the erythrocyte. [8]

Symporters

In contrast to antiporters, symporters move ions or molecules in the same direction. [1] In this case both ions being transported will be moved either from the exoplasmic space into the cytoplasmic space or from the cytoplasmic space into the exoplasmic space. An example of a symporter is the sodium-glucose linked transporter or SGLT. The SGLT functions to couple the transport of sodium in the exoplasmic space down its concentration gradient (again, established by the active transport of sodium out of the cell by the sodium-potassium pump) into the cytoplasmic space to the transport of glucose in the exoplasmic space against its concentration gradient into the cytoplasmic space. The SGLT couples the movement of 1 glucose ion with the movement of 2 sodium ions. [9] [10]

Examples of cotransporters

Na+/glucose cotransporter (SGLT1) – is also known as sodium-glucose cotransporter 1 and is encoded by the SLC5A1 gene. SGLT1 is an electrogenic transporter as the sodium electrochemical gradient drives glucose uphill into the cells. SGLT1 is a high affinity Na+ /glucose cotransporter that has an important role in transferring sugar across the epithelial cells of renal proximal tubules and of the intestine, in particular the small intestine. [11] [12]

Na+/phosphate cotransporter (NaPi) – Sodium-phosphate cotransporters are from the SLC34 and SLC20 protein families. They are also found across the epithelial cells of renal proximal tubule and of the small intestine. It transfers inorganic phosphate into cells through active transport with the help of a Na+ gradient. Similar to SGTL1, they are classified as electrogenic transporters. NaPi coupled with 3 Na+ ions and 1 divalent Pi, are classified as NaPi IIa and NaPi IIb. NaPi that couples with 2 Na+ and 1 divalent Pi are classified as NaPi IIc. [11] [13]

Na+/I− symporter (NIS) – Sodium-Iodide is a type of symporter that is responsible for transferring iodide in the thyroid gland. NIS is primarily found in cells of the thyroid gland and also in the mammary glands. They are located on the basolateral membrane of thyroid follicular cells where 2 Na+ ions and 1 I− ion is coupled to transfer the iodide. NIS activity helps in the diagnosis and treatment of thyroid disease, including the highly successful treatment of thyroid cancer with radioiodide after thyroidectomy. [11] [14]

Na-K-2Cl symporter – This specific cotransporter regulates the cell volume by controlling the water and electrolyte content within the cell. [15] The Na-K-2Cl Cotransporter is vital in salt secretion in secretory epithelia cells along with renal salt reabsorption. [16] Two variations of the Na-K-2Cl symporter exist and are known as NKCC1 and NKCC2. The NKCC1 cotransport protein is found throughout the body but NKCC2 is found only in the kidney and removes the sodium, potassium, and chloride found in the body's urine, so it can be absorbed into the blood. [17]

GABA transporter (GAT) – neurotransmitter γ-aminobutyric acid (GABA) transporters are members of the solute carrier family 6 (SLC6) of sodium- and chloride-dependent neurotransmitter receptor transporters that are located in the plasma membrane and regulate the concentration of GABA in the synaptic cleft. The SLC6A1 gene encodes GABA transporters. [18] The transporters are electrogenic and couples 2 Na+, 1 Cl− and 1 GABA for inward translocation. [11] [19]

K+Cl− Symporter – The K+-Cl− cotransporter family consists of four specific symporters known as KCC1, KCC2, KCC3, and KCC4. The KCC2 isoform is specific to neuronal tissue and the other three can be found in various tissues throughout the body. This cotransporter family controls the concentration levels of potassium and chloride within cells through the combined movement of K+/H+ and Cl−/HCO3− exchangers or through combined movement of both ions due to concentration activated channels. The four known KCC proteins team up to form two separate subfamilies with KCC1 and KCC3 pairing together and KCC2 and KCC4 becoming a pair to facilitate ion movement. [20]

Associated diseases

Table 1: List of diseases related to transporters. [21]

Transporter Symbols/NamesRelevant Diseases
4F2HC, SLC3A2 Lysinuric
ABC-1, ABC1 Tangier disease
ABC7, hABC7X-linked sideroblastic anemia
ABCR Stargardt disease, Fundus flavimaculatus
AE1, SLC4A1 elliptocytosis, ovalocytosis, hemolytic anemia, spherocytosis, renal tubular acidosis
AE2, SLC4A2 congenital chloroidorrhea
AE3, SLC4A3congenital chloroidorrhea
ALDR Adrenoleukodystrophy
ANK ankylosis (calcification); arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction
Aralar-like, SLC25A13adult-onset type II citrullinemia
ATBo, SLC1A5, hATBo, ASCT2, AAAT Neurodegeneration
BCMP1, UCP4, SLC25A14HHH
CFTR Cystic fibrosis
CTR-1, SLC31A1Menkes/Wilsons disease
CTR-2, SLC31A2Menkes/Wilsons disease, X-linked hypophosphatemia
DTD, SLC26A2chondrodysplasias/ Diastrophic dysplasia
EAAT1, SLC1A3, GLAST1 Neurodegeneration, Amyotrophic lateral sclerosis
EAAT2, SLC1A2, GLT-1Neurodegeneration, Dicarboxylic aminoaciduria
EAAT3, SLC1A1, EAAC1Neurodegeneration
EAAT4, SLC1A6Neurodegeneration
EAAT5, SLC1A7Neurodegeneration
FIC1Progressive familial intrahepatic cholestasis
FOLT, SLC19A1, RFC1Folate malabsorption/megaloblastic anemia
GLUT1, SLC2A1low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus, defect in glucose transport across the blood-brain barrier
GLUT2, SLC2A2low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM)
GLUT3, SLC2A3low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM)
GLUT4, SLC2A4low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM)
GLUT5, SLC2A5Isolated fructose malabsorption
HET anemia, genetic hemochromatosis
HTT, SLC6A4anxiety-related traits
LAT-2, SLC7A6 Lysinuric protein intolerance
LAT-3, SLC7A7lysinuric protein intolerance
MDR1human cancers
MDR2, MDR3Familia intrahepatic cholestasis
MRP1human cancers
NBC Down syndrome
NBC1, SLC4A4renal tubular acidosis
NBC3, SLC4A7 congenital hypothyroidism
NCCT, SLC12A3, TSC Gitelman syndrome
NHE2, SLC9A2 Microvillus inclusion disease
NHE3, SLC9A3/3PMicrovillus inclusion disease
NIS, SLC5A5congenital hypothyroidism
NKCC1, SLC12A2 gitelman syndrome
NKCC2, SLC12A1 Bartter syndrome
NORTR DiGeorge syndrome, velocardiofacial syndrome
NRAMP2, DCT1, SLC11A2, Attention deficit hyperactivity disorder
NTCP2, ISBT, SLC10A2primary bile acid malabsorption (PBAM)
OCTN2, SLC22A5systemic carnitine deficiency (progressive cardiomyopathy, skeletal myopathy, hypoglycaemia, hyperammonaemia, sudden infant death syndrome)
ORNT1, SLC25A15HHH
PMP34, SLC25A17 Graves disease
rBAT, SLC3A1, D2 cystinuria
SATT, SLC1A4, ASCT1Neurodegeneration
SBC2hypocitraturia
SERTvarious mental disorders
SGLT1, SLC5A1renal glucosuria / glucose-galactose malabsorption
SGLT2, SLC5A2renal glucosuria
SMVT, SLC5A6anxiety-related traits, depression
TAP1juvenile onset psoriasis
y+L Type I cystinuria

See also

Related Research Articles

In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses adenosine triphosphate (ATP), and secondary active transport that uses an electrochemical gradient. This process is in contrast to passive transport, which allows molecules or ions to move down their concentration gradient, from an area of high concentration to an area of low concentration, without energy.

<span class="mw-page-title-main">Reuptake</span> Reabsorption of a neurotransmitter by a neurotransmitter transporter

Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal or glial cell after it has performed its function of transmitting a neural impulse.

<span class="mw-page-title-main">Mediated transport</span> Transportation of substances via membrane

Mediated transport refers to transport mediated by a membrane transport protein. Substances in the human body may be hydrophobic, electrophilic, contain a positively or negatively charge, or have another property. As such there are times when those substances may not be able to pass over the cell membrane using protein-independent movement. The cell membrane is imbedded with many membrane transport proteins that allow such molecules to travel in and out of the cell. There are three types of mediated transporters: uniport, symport, and antiport. Things that can be transported are nutrients, ions, glucose, etc, all depending on the needs of the cell. One example of a uniport mediated transport protein is GLUT1. GLUT1 is a transmembrane protein, which means it spans the entire width of the cell membrane, connecting the extracellular and intracellular region. It is a uniport system because it specifically transports glucose in only one direction, down its concentration gradient across the cell membrane.

A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion or active transport. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.

<span class="mw-page-title-main">Antiporter</span> Class of transmembrane transporter protein

An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell. Na+/H+ antiporters have been reviewed.

<span class="mw-page-title-main">Glucose transporter</span> Family of monosaccharide transport proteins

Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla. The GLUT or SLC2A family are a protein family that is found in most mammalian cells. 14 GLUTS are encoded by the human genome. GLUT is a type of uniporter transporter protein.

<span class="mw-page-title-main">Ion transporter</span> Transmembrane protein that moves ions across a biological membrane

In biology, a transporter is a transmembrane protein that moves ions across a biological membrane to accomplish many different biological functions including, cellular communication, maintaining homeostasis, energy production, etc. There are different types of transporters including, pumps, uniporters, antiporters, and symporters. Active transporters or ion pumps are transporters that convert energy from various sources—including adenosine triphosphate (ATP), sunlight, and other redox reactions—to potential energy by pumping an ion up its concentration gradient. This potential energy could then be used by secondary transporters, including ion carriers and ion channels, to drive vital cellular processes, such as ATP synthesis.

Method of glucose uptake differs throughout tissues depending on two factors; the metabolic needs of the tissue and availability of glucose. The two ways in which glucose uptake can take place are facilitated diffusion and secondary active transport. Active transport is the movement of ions or molecules going against the concentration gradient.

The galactose permease or GalP found in Escherichia coli is an integral membrane protein involved in the transport of monosaccharides, primarily hexoses, for utilization by E. coli in glycolysis and other metabolic and catabolic pathways (3,4). It is a member of the Major Facilitator Super Family (MFS) and is homologue of the human GLUT1 transporter (4). Below you will find descriptions of the structure, specificity, effects on homeostasis, expression, and regulation of GalP along with examples of several of its homologues.

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO Gene Nomenclature Committee (HGNC) and is the basis for the official HGNC names of the genes that encode these transporters. A more general transmembrane transporter classification can be found in TCDB database.

Sodium-dependent glucose cotransporters are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron. They contribute to renal glucose reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be reabsorbed along the nephron. If the plasma glucose concentration is too high (hyperglycemia), glucose passes into the urine (glucosuria) because SGLT are saturated with the filtered glucose.

The Na–K–Cl cotransporter (NKCC) is a transport protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes. Two isoforms of the NKCC1/Slc12a2 gene result from keeping or skipping exon 21 in the final gene product.

<span class="mw-page-title-main">Symporter</span>

A symporter is an integral membrane protein that is involved in the transport of two different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time, and is, therefore, a type of cotransporter. The transporter is called a symporter, because the molecules will travel in the same direction in relation to each other. This is in contrast to the antiport transporter. Typically, the ion(s) will move down the electrochemical gradient, allowing the other molecule(s) to move against the concentration gradient. The movement of the ion(s) across the membrane is facilitated diffusion, and is coupled with the active transport of the molecule(s). In symport, two molecule move in a 'similar direction' at the 'same time'. For example, the movement of glucose along with sodium ions.

<span class="mw-page-title-main">Sodium/glucose cotransporter 1</span>

Sodium/glucose cotransporter 1 (SGLT1) also known as solute carrier family 5 member 1 is a protein in humans that is encoded by the SLC5A1 gene which encodes the production of the SGLT1 protein to line the absorptive cells in the small intestine and the epithelial cells of the kidney tubules of the nephron for the purpose of glucose uptake into cells. Recently, it has been seen to have functions that can be considered as promising therapeutic target to treat diabetes and obesity. Through the use of the sodium glucose cotransporter 1 protein, cells are able to obtain glucose which is further utilized to make and store energy for the cell.

Renal reabsorption of sodium (Na+) is a part of renal physiology. It uses Na-H antiport, Na-glucose symport, sodium ion channels (minor). It is stimulated by angiotensin II and aldosterone, and inhibited by atrial natriuretic peptide.

<span class="mw-page-title-main">Robert K. Crane</span> American biochemist

Robert Kellogg Crane was an American biochemist best known for his discovery of sodium–glucose cotransport.

<span class="mw-page-title-main">Lactose permease</span>

Lactose permease is a membrane protein which is a member of the major facilitator superfamily. Lactose permease can be classified as a symporter, which uses the proton gradient towards the cell to transport β-galactosides such as lactose in the same direction into the cell.

<span class="mw-page-title-main">Sodium-solute symporter</span> Group of transport proteins

Members of the Solute:Sodium Symporter (SSS) Family (TC# 2.A.21) catalyze solute:Na+ symport. The SSS family is within the APC Superfamily. The solutes transported may be sugars, amino acids, organo cations such as choline, nucleosides, inositols, vitamins, urea or anions, depending on the system. Members of the SSS family have been identified in bacteria, archaea and eukaryotes. Almost all functionally well-characterized members normally catalyze solute uptake via Na+ symport.

<span class="mw-page-title-main">Bacterial Leucine Transporter</span>

Bacterial Leucine Transporter (LeuT) is a bundled twelve alpha helix protein which belongs to the family of transporters that shuttle amino acids in and out of bacterial cells. Specialized in small hydrophobic amino acids such as leucine and alanine, this transporter is powered by the gradient of sodium ions that is normally maintained by healthy cells across their membranes. LeuT acts as a symporter, which means that it links the passage of a sodium ion across the cell membrane with the transport of the amino acid in the same direction. It was first crystallized to understand the inner molecular mechanisms of antidepressant's work since it has a close resemblance with the human neurotransmitter transporters that these drugs block, thus inhibiting the reuptake of chemical messengers across the cell membrane of nerve axons and glial cells.

The anion exchanger family is a member of the large APC superfamily of secondary carriers. Members of the AE family are generally responsible for the transport of anions across cellular barriers, although their functions may vary. All of them exchange bicarbonate. Characterized protein members of the AE family are found in plants, animals, insects and yeast. Uncharacterized AE homologues may be present in bacteria. Animal AE proteins consist of homodimeric complexes of integral membrane proteins that vary in size from about 900 amino acyl residues to about 1250 residues. Their N-terminal hydrophilic domains may interact with cytoskeletal proteins and therefore play a cell structural role. Some of the currently characterized members of the AE family can be found in the Transporter Classification Database.

References

  1. 1 2 3 4 5 Lodish, Harvey; Berk, A.; Amon, A.; Bretscher, A.; Kaiser, C.; Kriefer, M.; et al. (2013). Molecular cell biology (7th ed.). New York: W.H. Freeman and Co. ISBN   978-1-4292-3413-9.
  2. 1 2 Chrispeels, Maarten J.; Nigel M. Crawford; Julian I. Schroeder (April 1999). "Proteins for Transport of Water and Mineral Nutrients across the Membranes of Plant Cells". The Plant Cell. 11 (4): 661–675. doi:10.1105/tpc.11.4.661. PMC   144211 . PMID   10213785.
  3. ↑ Zhao, Feng-Qi; Aileen F. Keating (2007). "Functional Properties and Genomics of Glucose Transporters". Current Genomics. 8 (2): 113–128. doi:10.2174/138920207780368187. PMC   2435356 . PMID   18660845.
  4. ↑ Hamilton, Kirk L. (March 2013). "Robert K. Crane—Na+-glucose cotransporter to cure?". Frontiers in Physiology. 4 (53): 53. doi: 10.3389/fphys.2013.00053 . PMC   3605518 . PMID   23525627.
  5. 1 2 Longpré, JP; Lapointe, JY (Jan 5, 2011). "Determination of the Na+/glucose cotransporter (SGLT1) turnover rate using the ion-trap technique". Biophysical Journal. 100 (1): 52–9. Bibcode:2011BpJ...100...52L. doi:10.1016/j.bpj.2010.11.012. PMC   3010014 . PMID   21190656.
  6. ↑ Jardetzky, O (Aug 27, 1966). "Simple allosteric model for membrane pumps". Nature. 211 (5052): 969–70. Bibcode:1966Natur.211..969J. doi:10.1038/211969a0. PMID   5968307. S2CID   4178898.
  7. ↑ Blaustein, MP; Lederer, WJ (July 1999). "Sodium/calcium exchange: its physiological implications". Physiological Reviews. 79 (3): 763–854. doi:10.1152/physrev.1999.79.3.763. PMID   10390518. S2CID   6963309.
  8. ↑ Lodish, Harvey (2000). Molecular cell biology (4. ed., 1. print. ed.). New York: Freeman. ISBN   978-0716737063.
  9. ↑ Wright, Ernest; Eric Turk (February 2004). "The sodium/glucose cotransport family SLC5". Pflügers Archiv: European Journal of Physiology. 447 (5): 510–518. doi:10.1007/s00424-003-1063-6. PMID   12748858. S2CID   41985805.
  10. ↑ Chen, Xing-Zhen; Coady, Michael J.; Jackson, Francis; Berteloot, Alfred; Lapointe, Jean-Yves (December 1995). "Thermodynamic Determination of the Na+: Glucose Coupling Ratio for the Human SGLT1 Cotransporter". Biophysical Journal. 69 (6): 2405–2414. Bibcode:1995BpJ....69.2405C. doi:10.1016/s0006-3495(95)80110-4. PMC   1236478 . PMID   8599647.
  11. 1 2 3 4 Physiologyweb. "Secondary Active Transport". Physiologyweb. Retrieved 4 December 2013.
  12. ↑ Wright, Ernest M.; Donald D. F. Loo; Bruce A. Hirayama; Eric Turk (December 2004). "Surprising Versatility of Na+-Glucose Cotransporters: SLC5". Physiology. 19 (6): 370–376. doi:10.1152/physiol.00026.2004. PMID   15546855.
  13. ↑ Biber, Jürg; Nati Hernando; Ian Forster (2013). "Phosphate Transporters and Their Function". Annual Review of Physiology. 75 (1): 535–550. doi:10.1146/annurev-physiol-030212-183748. PMID   23398154.
  14. ↑ Paroder-Belenitsky, Monika; Maestas, Matthew J.; Dohán, Orsolya; Nicola, Juan Pablo; Reyna-Neyra, Andrea; Follenzi, Antonia; Dadachova, Ekaterina; Eskandari, Sepehr; Amzel, L. Mario; Carrasco, Nancy (November 2011). "Mechanism of anion selectivity and stoichiometry of the Na+/I− symporter (NIS)". PNAS. 108 (44): 17933–17938. Bibcode:2011PNAS..10817933P. doi: 10.1073/pnas.1108278108 . PMC   3207644 . PMID   22011571.
  15. ↑ Lionetto, MG; Schettino, T (May–Jun 2006). "The Na+-K+-2Cl− cotransporter and the osmotic stress response in a model salt transport epithelium". Acta Physiologica. 187 (1–2): 115–24. doi:10.1111/j.1748-1716.2006.01536.x. PMID   16734748. S2CID   42069918.
  16. ↑ Haas, M (October 1994). "The Na-K-Cl cotransporters". The American Journal of Physiology. 267 (4 Pt 1): C869–85. doi:10.1152/ajpcell.1994.267.4.C869. PMID   7943281.
  17. ↑ Hebert, SC; Mount, DB; Gamba, G (February 2004). "Molecular physiology of cation-coupled Cl− cotransport: the SLC12 family". Pflügers Archiv: European Journal of Physiology. 447 (5): 580–93. doi:10.1007/s00424-003-1066-3. PMID   12739168. S2CID   21998913.
  18. ↑ OMIM Entry. "137165 - SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GABA), MEMBER 1; SLC6A1". Johns Hopkins University. Retrieved 8 December 2013.
  19. ↑ GeneCads. "SLC6A11 Gene". Weizmann Institute of Science. Retrieved 8 December 2013.
  20. ↑ Mercado, A; Song, L; Vazquez, N; Mount, DB; Gamba, G (Sep 29, 2000). "Functional comparison of the K+-Cl− cotransporters KCC1 and KCC4". The Journal of Biological Chemistry. 275 (39): 30326–34. doi: 10.1074/jbc.M003112200 . PMID   10913127.
  21. ↑ "Membrane Transporter-Related Diseases « Membrane Transporter Database for Personalized Medicine". pharmtao.com.
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