Editing Hemoglobin (section)

==Research history==
[[File:Max Perutz.jpg|thumb|upright|[[Max Perutz]] won the [[Nobel Prize for chemistry]] for his work determining the molecular structure of hemoglobin and [[myoglobin]]<ref>{{cite news |title=Max Perutz, Father of Molecular Biology, Dies at 87 |website=The New York Times |date=2002-02-08 |url=https://www.nytimes.com/2002/02/08/world/max-perutz-father-of-molecular-biology-dies-at-87.html |archive-url=https://web.archive.org/web/20160423072418/https://www.nytimes.com/2002/02/08/world/max-perutz-father-of-molecular-biology-dies-at-87.html |archive-date=2016-04-23}}</ref>]]
In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species.<ref name="Engelhart-1825">{{cite book |last=Engelhart |first=Johann Friedrich |title=Commentatio de vera materia sanguini purpureum colorem impertientis natura |year=1825 |publisher=Dietrich |location=Göttingen |language=la |url=https://opacplus.bsb-muenchen.de/Vta2/bsb10972513/bsb:BV006399484?page=1 |access-date=2020-06-16 |url-status=live |archive-url=https://web.archive.org/web/20200616114253/https://opacplus.bsb-muenchen.de/Vta2/bsb10972513/bsb:BV006399484?page=1 |archive-date=2020-06-16}}</ref><ref name="Edinburgh Medical and Surgical Journal-1827">{{cite journal |title=Engelhard & Rose on the Colouring Matter of the Blood |journal=Edinburgh Medical and Surgical Journal |volume=27 |number=90 |pages=95–102 |date=1827 |pmid=30330061 |pmc=5763191}}</ref> From the known atomic mass of iron, he calculated the molecular mass of hemoglobin to ''n'' × 16000 (''n''=number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a protein's molecular mass. This "hasty conclusion" drew ridicule from colleagues who could not believe that any molecule could be so large. However, [[Gilbert Smithson Adair]] confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions.<ref>{{cite journal |last=Adair |first=Gilbert Smithson |title=A critical study of the direct method of measuring the osmotic pressure of hǣmoglobin |journal=Proc. R. Soc. Lond. |year=1925 |volume=108 |issue=750 |pages=292–300 |bibcode=1925RSPSA.109..292A |doi=10.1098/rspa.1925.0126 |doi-access=free}}</ref>

Although blood had been known to carry oxygen since at least 1794,<ref>{{cite book |last=Parry |first=CH |title=Letters from Dr. Withering, ... Dr. Ewart, ... Dr. Thorton ... and Dr. Biggs ... together with some other papers, supplementary to two publications on asthma, consumption, fever, and other diseases, by T. Beddoes |date=1794 |pages=43 |language=en |url=https://books.google.com/books?id=XkxpAAAAcAAJ&q=factitious |access-date=2021-11-30 |url-status=live |archive-url=https://web.archive.org/web/20220131131255/https://books.google.com/books?id=XkxpAAAAcAAJ&q=factitious |archive-date=2022-01-31}}</ref><ref>{{cite book |last=Beddoes |first=T. |title=Considerations on the Medicinal Use, and on the Production of Factitious Airs: Part I. By Thomas Beddoes, M.D. Part II. By James Watt, Engineer; "Part 1, section 2, "Of the breathing of man and familiar animals" |date=1796 |publisher=Bulgin and Rosser |at=Part 1, p. 9–13 |language=en |url=https://books.google.com/books?id=iAg2AQAAMAAJ&dq=cavendish&pg=PA31 |access-date=2021-11-30 |url-status=live |archive-url=https://web.archive.org/web/20220131131252/https://books.google.com/books?id=iAg2AQAAMAAJ&dq=cavendish&pg=PA31 |archive-date=2022-01-31}}</ref> the oxygen-carrying property of hemoglobin was described by Hünefeld in 1840.<ref>{{cite book |last1=Hünefeld |first1=Friedrich Ludwig |title=Der Chemismus in der thierischen Organisation |date=1840 |publisher=F. A. Brockhaus |location=Leipzig |language=de |url=https://www.digitale-sammlungen.de/de/view/bsb10368567?page=7 |access-date=26 February 2021 |url-status=live |archive-url=https://web.archive.org/web/20210414105616/https://reader.digitale-sammlungen.de/de/fs1/object/display/bsb10368567_00007.html |archive-date=14 April 2021}}</ref> In 1851, German physiologist [[Otto Funke]] published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution.<ref name="Funke-1851">{{cite journal |author=Funke O |title=Über das milzvenenblut |journal=Z Rat Med |volume=1 |pages=172–218 |year=1851}}</ref><ref>{{cite web |title=A NASA Recipe For Protein Crystallography |website=Educational Brief |publisher=National Aeronautics and Space Administration |url=https://www.okcareertech.org/cimc/special/nochild/downloads/science/Protein.Crystallography.pdf |access-date=2008-10-12 |archive-url=https://web.archive.org/web/20080410161517/https://www.okcareertech.org/cimc/special/nochild/downloads/science/Protein.Crystallography.pdf |archive-date=2008-04-10}}</ref> Hemoglobin's reversible oxygenation was described a few years later by [[Felix Hoppe-Seyler]].<ref name="Hoppe-Seyler-1866">{{cite journal |author=Hoppe-Seyler F |title=Über die oxydation in lebendem blute |journal=Med-chem Untersuch Lab |volume=1 |pages=133–40 |year=1866}}</ref>

With the development of [[X-ray crystallography]], it became possible to solve protein structures.<ref name="Stoddart-2022">{{cite journal |last1=Stoddart |first1=Charlotte |title=Structural biology: How proteins got their close-up |journal=Knowable Magazine |date=1 March 2022 |doi=10.1146/knowable-022822-1 |doi-access=free |url=https://knowablemagazine.org/article/living-world/2022/structural-biology-how-proteins-got-their-closeup |access-date=25 March 2022}}</ref> In 1959, [[Max Perutz]] determined the molecular structure of hemoglobin.<ref name="Perutz-1960a">{{cite journal |last1=Perutz |first1=M.F. |last2=Rossmann |first2=M.G. |last3=Cullis |first3=A.F. |last4=Muirhead |first4=H. |last5=Will |first5=G. |last6=North |first6=A.C.T. |year=1960 |title=Structure of haemoglobin: a three-dimensional Fourier synthesis at 5.5-A. resolution, obtained by X-ray analysis |journal=Nature |volume=185 |issue=4711 |pages=416–22 |bibcode=1960Natur.185..416P |pmid=18990801 |doi=10.1038/185416a0 |s2cid=4208282}}</ref><ref name="Perutz-1960b">{{cite journal |author=Perutz MF |title=Structure of haemoglobin |journal=Brookhaven Symposia in Biology |volume=13 |pages=165–83 |year=1960 |pmid=13734651}}</ref> For this work he shared the 1962 [[Nobel Prize in Chemistry]] with [[John Kendrew]], who sequenced the globular protein [[myoglobin]].<ref name="Stoddart-2022"/><ref name="de Chadarevian-2018">{{cite journal |last1=de Chadarevian |first1=Soraya |title=John Kendrew and myoglobin: Protein structure determination in the 1950s: John Kendrew and Myoglobin |journal=Protein Science |date=June 2018 |volume=27 |issue=6 |pages=1136–1143 |pmid=29607556 |doi=10.1002/pro.3417 |pmc=5980623}}</ref>

The role of hemoglobin in the blood was elucidated by French [[physiologist]] [[Claude Bernard]].

The name ''hemoglobin'' (or ''haemoglobin'') is derived from the words ''[[heme]]'' (or ''[[heme|haem]]'') and ''[[globin]]'', reflecting the fact that each [[protein subunit|subunit]] of hemoglobin is a [[globular protein]] with an embedded [[heme]] group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits.<ref>{{Cite journal |last1=Nishi |first1=Hiroshi |last2=Inagi |first2=Reiko |last3=Kato |first3=Hideki |last4=Tanemoto |first4=Masayuki |last5=Kojima |first5=Ichiro |last6=Son |first6=Daisuke |last7=Fujita |first7=Toshiro |last8=Nangaku |first8=Masaomi |date=August 2008 |title=Hemoglobin Is Expressed by Mesangial Cells and Reduces Oxidant Stress |journal=Journal of the American Society of Nephrology |volume=19 |issue=8 |pages=1500–1508 |doi=10.1681/ASN.2007101085 |issn=1046-6673 |pmc=2488266 |pmid=18448584}}</ref>