Editing Active transport (section)

==Secondary active transport==
In secondary active transport, also known as [[Cotransporter|cotransport or coupled transport]], energy is used to transport molecules across a membrane; however, in contrast to [[primary active transport]], there is no direct coupling of [[Adenosine triphosphate|ATP]]. Instead, it relies upon the [[electrochemical potential|electrochemical potential difference]] created by pumping ions in/out of the cell.<ref>{{cite book| title= Essentials of Human Physiology| first= Thomas M. |last= Nosek| chapter=Section 7/7ch05/7ch05p12 |chapter-url=http://humanphysiology.tuars.com/program/section7/7ch05/7ch05p12.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section7/7ch05/7ch05p12.htm|archive-date=2016-03-24}}</ref> Permitting one ion or molecule to move down an electrochemical gradient, but possibly against the concentration gradient where it is more concentrated to that where it is less concentrated, increases [[entropy]] and can serve as a source of [[energy]] for [[metabolism]] (e.g. in [[ATP synthase]]). The energy derived from the pumping of protons across a cell membrane is frequently used as the energy source in secondary active transport. In humans, sodium (Na<sup>+</sup>) is a commonly cotransported ion across the plasma membrane, whose electrochemical gradient is then used to power the active transport of a second ion or molecule against its gradient.<ref name="Alberts B 2002">Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. [https://www.ncbi.nlm.nih.gov/books/NBK26896/ Carrier Proteins and Active Membrane Transport].</ref> In bacteria and small yeast cells, a commonly cotransported ion is hydrogen.<ref name="Alberts B 2002"/> Hydrogen pumps are also used to create an electrochemical gradient to carry out processes within cells such as in the [[electron transport chain]], an important function of [[cellular respiration]] that happens in the [[mitochondrion]] of the cell.<ref>Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. [https://www.ncbi.nlm.nih.gov/books/NBK26904/ Electron-Transport Chains and Their Proton Pumps].</ref>

In August 1960, in Prague, [[Robert K. Crane]] presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.<ref>{{cite book |author-link=Robert K. Crane |first1=Robert K. |last1=Crane |first2=D. |last2=Miller |first3=I. |last3=Bihler |chapter=The restrictions on possible mechanisms of intestinal transport of sugars |editor=Kleinzeller, A. |editor2=Kotyk, A. |title=Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960 |publisher=[[Academy of Sciences of the Czech Republic|Czech Academy of Sciences]] |location=Prague |year=1961 |pages=439–449 }}</ref> Crane's discovery of cotransport was the first ever proposal of flux coupling in biology.<ref>{{cite journal |vauthors=Wright EM, Turk E |title=The sodium/glucose cotransport family SLC5 |journal=Pflügers Arch. |volume=447 |issue=5 |pages=510–8 |date=February 2004 |pmid=12748858 |doi= 10.1007/s00424-003-1063-6 |s2cid=41985805 |quote=[[Robert K. Crane|Crane]] in 1961 was the first to formulate the cotransport concept to explain active transport [7]. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was coupled to downhill {{chem|Na|+}} transport cross the brush border. This hypothesis was rapidly tested, refined and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type.}}</ref><ref>{{cite journal |author =Boyd CA |title=Facts, fantasies and fun in epithelial physiology |journal=Exp. Physiol. |volume=93 |issue=3 |pages=303–14 (304) |date=March 2008 |pmid=18192340 |doi=10.1113/expphysiol.2007.037523 |quote= the insight from this time that remains in all current text books is the notion of [[Robert K. Crane|Robert Crane]] published originally as an appendix to a symposium paper published in 1960 ([[Robert K. Crane|Crane]] et al. 1960). The key point here was 'flux coupling', the cotransport of sodium and glucose in the apical membrane of the small intestinal epithelial cell. Half a century later this idea has turned into one of the most studied of all transporter proteins (SGLT1), the sodium–glucose cotransporter.|doi-access=free }}</ref>

[[Cotransporter]]s can be classified as [[symporter]]s and [[antiporter]]s depending on whether the substances move in the same or opposite directions.

===Antiporter===
[[Image:Porters.PNG|right|thumb|Function of [[symporter]]s and [[antiporter]]s.]]
In an antiporter two species of ions or other solutes are pumped in opposite directions across a membrane. One of these species is allowed to flow from high to low concentration, which yields the [[entropy|entropic energy]] to drive the transport of the other solute from a low concentration region to a high one.

An example is the [[sodium-calcium exchanger]] or [[antiporter]], which allows three sodium ions into the cell to transport one calcium out.<ref>{{cite journal|last1=Yu|first1=SP|last2=Choi|first2=DW|title=Na<sup>+</sup>-Ca<sup>2+</sup> exchange currents in cortical neurons: concomitant forward and reverse operation and effect of glutamate.|journal=The European Journal of Neuroscience|date=June 1997|volume=9|issue=6|pages=1273–81|pmid=9215711|doi=10.1111/j.1460-9568.1997.tb01482.x|s2cid=23146698}}</ref> This antiporter mechanism is important within the membranes of cardiac muscle cells in order to keep the calcium concentration in the cytoplasm low.<ref name="ncbi.nlm.nih.gov"/> Many cells also possess [[calcium ATPase]]s, which can operate at lower intracellular concentrations of calcium and sets the normal or resting concentration of this important [[second messenger]].<ref>{{cite journal|last1=Strehler|first1=EE|last2=Zacharias|first2=DA|s2cid=9062253|title=Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps.|journal=Physiological Reviews|date=January 2001|volume=81|issue=1|pages=21–50|pmid=11152753|doi=10.1152/physrev.2001.81.1.21}}</ref> But the ATPase exports calcium ions more slowly: only 30 per second versus 2000 per second by the exchanger. The exchanger comes into service when the calcium concentration rises steeply or "spikes" and enables rapid recovery.<ref>{{cite journal|last1=Patterson|first1=M|last2=Sneyd|first2=J|last3=Friel|first3=DD|title=Depolarization-induced calcium responses in sympathetic neurons: relative contributions from Ca<sup>2+</sup> entry, extrusion, ER/mitochondrial Ca<sup>2+</sup> uptake and release, and Ca<sup>2+</sup> buffering.|journal=The Journal of General Physiology|date=January 2007|volume=129|issue=1|pages=29–56|pmid=17190902|doi=10.1085/jgp.200609660|pmc=2151609}}</ref> This shows that a single type of ion can be transported by several enzymes, which need not be active all the time (constitutively), but may exist to meet specific, intermittent needs.

=== Symporter ===

A [[symporter]] uses the downhill movement of one [[Solution (chemistry)|solute species]] from high to low concentration to move another molecule uphill from low concentration to high concentration (against its [[concentration gradient]]). Both molecules are transported in the same direction.

An example is the glucose symporter [[Sodium-glucose transport proteins|SGLT1]], which co-transports one [[glucose]] (or [[galactose]]) molecule into the cell for every two sodium ions it imports into the cell.<ref>{{cite journal|last1=Wright|first1=EM|last2=Loo|first2=DD|last3=Panayotova-Heiermann|first3=M|last4=Lostao|first4=MP|last5=Hirayama|first5=BH|last6=Mackenzie|first6=B|last7=Boorer|first7=K|last8=Zampighi|first8=G|title='Active' sugar transport in eukaryotes.|journal=The Journal of Experimental Biology|date=November 1994|volume=196|pages=197–212|doi=10.1242/jeb.196.1.197|pmid=7823022}}</ref> This [[symporter]] is located in the small intestines,<ref>{{cite journal|last1=Dyer|first1=J|last2=Hosie|first2=KB|last3=Shirazi-Beechey|first3=SP|title=Nutrient regulation of human intestinal sugar transporter (SGLT2) expression.|journal=Gut|date=July 1997|volume=41|issue=1|pages=56–9|pmid=9274472|doi=10.1136/gut.41.1.56|pmc=1027228}}</ref> heart,<ref>{{cite journal|last1=Zhou|first1=L|last2=Cryan|first2=EV|last3=D'Andrea|first3=MR|last4=Belkowski|first4=S|last5=Conway|first5=BR|last6=Demarest|first6=KT|title=Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT2).|journal=Journal of Cellular Biochemistry|date=1 October 2003|volume=90|issue=2|pages=339–46|pmid=14505350|doi=10.1002/jcb.10631|s2cid=21908010}}</ref> and brain.<ref>{{cite journal|last1=Poppe|first1=R|last2=Karbach|first2=U|last3=Gambaryan|first3=S|last4=Wiesinger|first4=H|last5=Lutzenburg|first5=M|last6=Kraemer|first6=M|last7=Witte|first7=OW|last8=Koepsell|first8=H|title=Expression of the Na+-D-glucose cotransporter SGLT1 in neurons.|journal=Journal of Neurochemistry|date=July 1997|volume=69|issue=1|pages=84–94|pmid=9202297|doi=10.1046/j.1471-4159.1997.69010084.x|s2cid=34558770|doi-access=free}}</ref> It is also located in the S3 segment of the [[proximal tubule]] in each [[nephron]] in the [[kidney]]s.<ref>{{cite journal|author =Wright EM|year=2001|title=Renal Na<sup>+</sup>-glucose cotransporters|journal=Am J Physiol Renal Physiol|pmid=11133510|volume=280|issue=1|pages=F10–8|doi=10.1152/ajprenal.2001.280.1.F10}}</ref>  Its mechanism is exploited in [[Oral rehydration therapy|glucose rehydration therapy]]<ref name="pmid8917597">{{cite journal|last1=Loo|first1=DD|last2=Zeuthen|first2=T|last3=Chandy|first3=G|last4=Wright|first4=EM|title=Cotransport of water by the Na+/glucose cotransporter.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=12 November 1996|volume=93|issue=23|pages=13367–70|pmid=8917597|doi=10.1073/pnas.93.23.13367|pmc=24099|bibcode=1996PNAS...9313367L|doi-access=free}}</ref> This mechanism uses the absorption of sugar through the walls of the intestine to pull water in along with it.<ref name="pmid8917597" /> Defects in SGLT2 prevent effective reabsorption of glucose, causing [[Glucosuria|familial renal glucosuria]].<ref>{{cite journal|vauthors=Wright EM, Hirayama BA, Loo DF |year=2007|title=Active sugar transport in health and disease|pmid=17222166|volume=261|issue=1|pages=32–43|doi=10.1111/j.1365-2796.2006.01746.x|journal=Journal of Internal Medicine|doi-access=}}</ref>