Editing Red blood cell (section)

== Function ==

===Role in {{CO2}} transport===

Recall that [[Respiration (physiology)|respiration]], as illustrated schematically here with a unit of carbohydrate, produces about as many molecules of carbon dioxide, CO<sub>2</sub>, as it consumes of oxygen, O<sub>2</sub>.<ref name="guyton">{{cite book | vauthors = Guyton AC |title=Textbook of Medical Physiology |date=1976 |publisher=W. B. Saunders |location=Philadelphia, PA |isbn=0-7216-4393-0 |pages=556 |edition=Fifth |chapter=Ch. 41 Transport of Oxygen and Carbon Dioxide in the Blood and Body Fluids |quote=The Respiratory Exchange Ratio is 1:1 when carbohydrate is consumed, it is as low as 0.7 when fat is consumed.}}</ref>

:<chem>HCOH + O2 -> CO2 + H2O</chem>

Thus, the function of the circulatory system is as much about the transport of carbon dioxide as about the transport of oxygen.
As stated elsewhere in this article, most of the carbon dioxide in the blood is in the form of bicarbonate ion. The bicarbonate provides a [[Bicarbonate buffer system|critical pH buffer]].<ref name="west1">{{cite book | vauthors = West JB |title=Respiratory Physiology – the essentials |date=1974 |publisher=Williams & Wilkens |location=Baltimore, MD |isbn=0-683-08932-3 |page=80 |chapter=Gas Transport to the Periphery |quote=Acid Base Status: The transport of CO2 has a profound effect on the acid-base status of blood and the body as a whole. The lung excretes over 10,000 mEq of carbonic acid per day compared to less than 100 mEq of fixed acids by the kidney.}}</ref> Thus, unlike hemoglobin for O<sub>2</sub> transport, there is a physiological advantage to not having a specific CO<sub>2</sub> transporter molecule.

Red blood cells, nevertheless, play a key role in the CO<sub>2</sub> transport process, for two reasons.
First, because, besides hemoglobin, they contain a large number of copies of the enzyme [[carbonic anhydrase]] on the inside of their cell membrane.<ref name="guyton6">{{cite book | vauthors = Guyton AC |title=Textbook of Medical Physiology |date=1976 |publisher=W. B. Saunders |location=Philadelphia, PA |isbn=0-7216-4393-0 |pages=553–554 |edition=Fifth |chapter=Ch. 41 Transport of Oxygen and Carbon Dioxide in the Blood and Body Fluids |quote=Reaction of Carbon Dioxide with Water in the Red Blood Cells - Effect of Carbonic Anhydrase}}</ref> Carbonic anhydrase, as its name suggests, acts as a catalyst of the exchange between [[carbonic acid]] and carbon dioxide (which is the [[acid anhydride|anhydride]] of carbonic acid). Because it is a catalyst, it can affect many CO<sub>2</sub> molecules, so it performs its essential role without needing as many copies as are needed for O<sub>2</sub> transport by hemoglobin.
In the presence of this catalyst carbon dioxide and carbonic acid reach an [[Henderson–Hasselbalch equation|equilibrium]] very rapidly, while the red cells are still moving through the capillary. Thus it is the RBC that ensures that most of the CO<sub>2</sub> is transported as bicarbonate.<ref name="guyton3">{{cite book | vauthors = Guyton AC |title=Textbook of Medical Physiology |date=1976 |publisher=W. B. Saunders |location=Philadelphia, PA |isbn=0-7216-4393-0 |pages=553–554 |edition=Fifth |chapter=Ch. 41 Transport of Oxygen and Carbon Dioxide in the Blood and Body Fluids |quote=carbonic anhydrase catalyzes the reaction between carbon dioxide and water.}}</ref><ref name="comroe">{{cite book | vauthors = Comroe Jr JH |title=Physiology of Respiration |date=1965 |publisher=Year Book Medical Publishers |location=Chicago, IL |isbn=0-8151-1824-4 |page=176 |edition=1971 |chapter=Transport and elimination of carbon dioxide |quote=[carbonic anhdrase] makes the reaction go to the right about 13000 times as fast}}</ref>
At physiological pH the equilibrium strongly favors carbonic acid, which is mostly dissociated into bicarbonate ion.<ref name="documenta">{{cite book | veditors = Diem K, Lentner C |title=Documenta Geigy Scientific Tables |date=1970 |publisher=Ciba-Geigy Limited |location=Basle, Switzerland |pages=570–571 |edition=7th |chapter=Blood Gasses |quote=In plasma about 5% of CO2 is in physical solution 94% as bicarbonate and 1% as carbamino compounds; in the erythrocytes the corresponding figures are 7%, 82% and 11%.}}</ref>

:<chem>CO2 + H2O <=>> H2CO3 <=>> HCO3- + H+ </chem>

The H+ ions released by this rapid reaction within RBC, while still in the capillary, act to reduce the oxygen binding affinity of hemoglobin, the [[Bohr effect]].

The second major contribution of RBC to carbon dioxide transport is that carbon dioxide directly reacts with globin protein components of hemoglobin to form [[carbaminohemoglobin]] compounds.
As oxygen is released in the tissues, more CO<sub>2</sub> binds to hemoglobin, and as oxygen binds in the lung, it displaces the hemoglobin bound CO<sub>2</sub>, this is called the [[Haldane effect]]. Despite the fact that only a small amount of the CO<sub>2</sub> in blood is bound to hemoglobin in venous blood, a greater proportion of the change in CO<sub>2</sub> content between venous and arterial blood comes from the change in this bound CO<sub>2</sub>.<ref name="guyton4">{{cite book | vauthors = Guyton AC |title=Textbook of Medical Physiology |date=1976 |publisher=W. B. Saunders |location=Philadelphia, PA |isbn=0-7216-4393-0 |page=554 |edition=Fifth |chapter=Ch. 41 Transport of Oxygen and Carbon Dioxide in the Blood and Body Fluids |quote=from figure 41-5 Hgb.CO2 is about 23% and bicarbonate is about 70% of the total carbon dioxide transported to the lungs.}}</ref> That is, there is always an abundance of bicarbonate in blood, both venous and arterial, because of its aforementioned role as a pH buffer.

In summary, carbon dioxide produced by cellular respiration diffuses very rapidly to areas of lower concentration, specifically into nearby capillaries.<ref name="comroe2">{{cite book | vauthors = Comroe J |title=Physiology of Respiration |date=1965 |publisher=Year Book Medical Publishers |location=Chicago, IL |isbn=0-8151-1824-4 |page=140 |edition=1971 |ref=comroe |chapter=Pulmonary Gas Diffusion |quote=Despite being a heavier molecule, because it is more soluble, the relative rate of diffusion of CO2 is about 20 times the rate of O2}}</ref><ref name="guyton5">{{cite book | vauthors = Guyton AC |title=Textbook of Medical Physiology |date=1976 |publisher=W. B. Saunders |location=Philadelphia, PA |isbn=0-7216-4393-0 |page=553 |edition=Fifth |chapter=Ch. 41 Transport of Oxygen and Carbon Dioxide in the Blood and Body Fluids |quote=carbon dioxide diffuses out of the tissue cells in the gaseous form (but not to a significant effect in the bicarbonate form because the cell membrane is far less permeable to bicarbonate than to the dissolved gas.}}</ref>
When it diffuses into a RBC, CO<sub>2</sub> is rapidly converted by the carbonic anhydrase found on the inside of the RBC membrane into bicarbonate ion. The bicarbonate ions in turn leave the RBC in exchange for [[chloride shift|chloride ions]] from the plasma, facilitated by the [[band 3 anion transport protein]] colocated in the RBC membrane. The bicarbonate ion does not diffuse back out of the capillary, but is carried to the lung. In the lung the lower [[partial pressure]] of carbon dioxide in the alveoli causes carbon dioxide to diffuse rapidly from the capillary into the alveoli. The carbonic anhydrase in the red cells keeps the bicarbonate ion in equilibrium with carbon dioxide. So as carbon dioxide leaves the capillary, and CO<sub>2</sub> is displaced by O<sub>2</sub> on hemoglobin, sufficient bicarbonate ion converts rapidly to carbon dioxide to maintain the equilibrium.<ref name="guyton6"/><ref name="comroe3">{{cite book | vauthors = Comroe Jr JH|title=Physiology of Respiration |date=1965 |publisher=Year Book Medical Publishers |location=Chicago, IL |isbn=0-8151-1824-4 |pages=175–177 |edition=1971 |ref=comroe |chapter=Transport and elimination of carbon dioxide |quote=the buffering occurred in the red cell}}</ref><ref name="west">{{cite book | vauthors = West JB |title=Respiratory Physiology – the essentials |date=1974 |publisher=Williams & Wilkens |location=Baltimore, MD |isbn=0-683-08932-3 |pages=77–79 |chapter=Gas Transport to the Periphery |quote=CO<sub>2</sub> Transport}}</ref><ref name="brobeck2">{{cite book | vauthors = Stone WE | veditors = Brobeck JR |title=Best & Taylor's Physiological basis of medical practice. |date=1973 |publisher=Williams & Wilkins |location=Baltimore, MD |isbn=0-683-10160-9 |pages=6.16–6.18 |edition=9th |ref=brobeck |chapter=Ch. 6-1 Uptake and Delivery of the Respiratory Gasses |quote=Transport of CO<sub>2</sub> as Bicarbonate}}</ref>

===Secondary functions===
When red blood cells undergo [[shear stress]] in constricted vessels, they release [[adenosine triphosphate|ATP]], which causes the vessel walls to relax and dilate so as to promote normal blood flow.<ref>{{cite journal | vauthors = Wan J, Ristenpart WD, Stone HA | title = Dynamics of shear-induced ATP release from red blood cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 43 | pages = 16432–16437 | date = October 2008 | pmid = 18922780 | pmc = 2575437 | doi = 10.1073/pnas.0805779105 | doi-access = free | bibcode = 2008PNAS..10516432W }}</ref>

When their hemoglobin molecules are deoxygenated, red blood cells release [[S-Nitrosothiol]]s, which also act to dilate blood vessels,<ref>{{cite journal | vauthors = Diesen DL, Hess DT, Stamler JS | title = Hypoxic vasodilation by red blood cells: evidence for an s-nitrosothiol-based signal | journal = Circulation Research | volume = 103 | issue = 5 | pages = 545–553 | date = August 2008 | pmid = 18658051 | pmc = 2763414 | doi = 10.1161/CIRCRESAHA.108.176867 }}</ref> thus directing more blood to areas of the body depleted of oxygen.

Red blood cells can also synthesize [[nitric oxide]] enzymatically, using [[L-arginine]] as substrate, as do [[endothelial cell]]s.<ref>{{cite journal | vauthors = Kleinbongard P, Schulz R, Rassaf T, Lauer T, Dejam A, Jax T, Kumara I, Gharini P, Kabanova S, Ozüyaman B, Schnürch HG, Gödecke A, Weber AA, Robenek M, Robenek H, Bloch W, Rösen P, Kelm M | display-authors = 6 | title = Red blood cells express a functional endothelial nitric oxide synthase | journal = Blood | volume = 107 | issue = 7 | pages = 2943–2951 | date = April 2006 | pmid = 16368881 | doi = 10.1182/blood-2005-10-3992 | name-list-style = vanc | s2cid = 38270024 | doi-access = free }}</ref> Exposure of red blood cells to physiological levels of shear stress activates [[nitric oxide synthase]] and export of nitric oxide,<ref>{{cite journal | vauthors = Ulker P, Sati L, Celik-Ozenci C, Meiselman HJ, Baskurt OK | title = Mechanical stimulation of nitric oxide synthesizing mechanisms in erythrocytes | journal = Biorheology | volume = 46 | issue = 2 | pages = 121–132 | year = 2009 | pmid = 19458415 | doi = 10.3233/BIR-2009-0532 }}</ref> which may contribute to the regulation of vascular tonus.

Red blood cells can also produce [[hydrogen sulfide]], a signalling gas that acts to relax vessel walls. It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide.<ref>{{cite journal | vauthors = Benavides GA, Squadrito GL, Mills RW, Patel HD, Isbell TS, Patel RP, Darley-Usmar VM, Doeller JE, Kraus DW | display-authors = 6 | title = Hydrogen sulfide mediates the vasoactivity of garlic | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 46 | pages = 17977–17982 | date = November 2007 | pmid = 17951430 | pmc = 2084282 | doi = 10.1073/pnas.0705710104 | author-link2 = Victor Darley-Usmar | doi-access = free | bibcode = 2007PNAS..10417977B }}</ref>

Red blood cells also play a part in the body's [[immune response]]: when [[lysis|lysed]] by pathogens such as bacteria, their hemoglobin releases [[free radical]]s, which break down the pathogen's cell wall and membrane, killing it.<ref>{{cite news| vauthors = Kesava S |title=Red blood cells do more than just carry oxygen; New findings by NUS team show they aggressively attack bacteria too|url=http://www.dbs.nus.edu.sg/events/media/info/2007/dingSTsep07.pdf|access-date=26 March 2013|newspaper=The Straits Times|date=1 September 2007}}</ref><ref>{{cite journal | vauthors = Jiang N, Tan NS, Ho B, Ding JL | title = Respiratory protein-generated reactive oxygen species as an antimicrobial strategy | journal = Nature Immunology | volume = 8 | issue = 10 | pages = 1114–1122 | date = October 2007 | pmid = 17721536 | doi = 10.1038/ni1501 | s2cid = 11359246 }}</ref>

=== Cellular processes ===
As a result of not containing [[mitochondrion|mitochondria]], red blood cells use none of the oxygen they transport; instead they produce the energy carrier [[Adenosine triphosphate|ATP]] by the [[glycolysis]] of [[glucose]] and [[lactic acid fermentation]] on the resulting [[pyruvate]].<ref>{{cite book|title=Biochemistry|date=2012|publisher=W.H. Freeman|isbn=9781429229364|edition=7th|location=New York|pages=455, 609| vauthors = Berg JM, Tymoczko JL, Stryer L }}</ref><ref>{{cite journal | vauthors = Tilton WM, Seaman C, Carriero D, Piomelli S | title = Regulation of glycolysis in the erythrocyte: role of the lactate/pyruvate and NAD/NADH ratios | journal = The Journal of Laboratory and Clinical Medicine | volume = 118 | issue = 2 | pages = 146–152 | date = August 1991 | pmid = 1856577 }}</ref> Furthermore, the [[pentose phosphate pathway]] plays an important role in red blood cells; see [[glucose-6-phosphate dehydrogenase deficiency]] for more information.

As red blood cells contain no nucleus, [[protein biosynthesis]] is currently assumed to be absent in these cells.

Because of the lack of nuclei and organelles, mature red blood cells do not contain [[DNA]] and cannot synthesize any [[RNA]] (although it does contain RNAs),<ref name="Kabanova2009">{{cite journal | vauthors = Kabanova S, Kleinbongard P, Volkmer J, Andrée B, Kelm M, Jax TW | title = Gene expression analysis of human red blood cells | journal = International Journal of Medical Sciences | volume = 6 | issue = 4 | pages = 156–159 | year = 2009 | pmid = 19421340 | pmc = 2677714 | doi = 10.7150/ijms.6.156 }}</ref><ref name="Jain2022">{{cite journal | vauthors = Jain V, Yang WH, Wu J, Roback JD, Gregory SG, Chi JT | title = Single Cell RNA-Seq Analysis of Human Red Cells | journal = Frontiers in Physiology | volume = 13 | page = 828700 | year = 2022 | pmid = 35514346 | pmc = 9065680 | doi = 10.3389/fphys.2022.828700 | doi-access = free }}</ref> and consequently cannot divide and have limited repair capabilities.<ref name=Molecular_biology_of_the_cell>{{cite book|first1=Bruce|last1=Alberts|first2=Alexander|last2= Johnson|first3= Julian |last3=Lewis|first4= Martin|last4= Raff|first5= Keith|last5=Roberts|first6=Peter|last6= Walter |title=Molecular biology of the cell|chapter = Erythropoiesis Depends on the Hormone Erythropoietin|date=2002|publisher=Garland|location=New York|isbn=0-8153-4072-9|edition=4th|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK26919/#_A4157_|access-date=30 November 2023}}</ref> The inability to carry out [[protein synthesis]] means that no virus can evolve to target mammalian red blood cells.<ref>{{cite news|url=https://www.nytimes.com/2007/03/27/science/27viral.html|title=Scientists Explore Ways to Lure Viruses to Their Death| vauthors = Zimmer C |date=27 March 2007|newspaper=The New York Times|access-date=26 March 2013}}</ref> However, infection with [[parvovirus]]es (such as human [[parvovirus B19]]) can affect erythroid precursors while they still have DNA, as recognized by the presence of giant [[pronormoblast]]s with viral particles and [[inclusion bodies]], thus temporarily depleting the blood of reticulocytes and causing [[anemia]].<ref>{{cite journal | vauthors = Heegaard ED, Brown KE | title = Human parvovirus B19 | journal = Clinical Microbiology Reviews | volume = 15 | issue = 3 | pages = 485–505 | date = July 2002 | pmid = 12097253 | pmc = 118081 | doi = 10.1128/CMR.15.3.485-505.2002 | name-list-style = amp }}</ref>