Editing Oxidative phosphorylation (section)

== History ==
{{further|History of biochemistry|History of molecular biology}}
The field of oxidative phosphorylation began with the report in 1906 by [[Arthur Harden]] of a vital role for phosphate in cellular [[fermentation (biochemistry)|fermentation]], but initially only [[sugar phosphates]] were known to be involved.<ref>{{cite journal | vauthors = Harden A, Young WJ |title=The alcoholic ferment of yeast-juice |journal=Proceedings of the Royal Society |volume=B |issue=77 |pages=405–20 |year=1906 |doi=10.1098/rspb.1906.0029 |doi-access=free }}</ref> However, in the early 1940s, the link between the oxidation of sugars and the generation of ATP was firmly established by [[Herman Kalckar]],<ref>{{cite journal | vauthors = Kalckar HM | title = Origins of the concept oxidative phosphorylation | journal = Molecular and Cellular Biochemistry | volume = 5 | issue = 1–2 | pages = 55–63 | date = November 1974 | pmid = 4279328 | doi = 10.1007/BF01874172 | s2cid = 26999163 }}</ref> confirming the central role of ATP in energy transfer that had been proposed by [[Fritz Albert Lipmann]] in 1941.<ref>{{cite journal | vauthors = Lipmann F |title=Metabolic generation and utilization of phosphate bond energy |journal=Adv Enzymol |volume=1 |pages=99–162 |year=1941 |doi=10.4159/harvard.9780674366701.c141|isbn=9780674366701 }}</ref> Later, in 1949, Morris Friedkin and [[Albert L. Lehninger]] proved that the coenzyme NADH linked metabolic pathways such as the citric acid cycle and the synthesis of ATP.<ref>{{cite journal | vauthors = Friedkin M, Lehninger AL | title = Esterification of inorganic phosphate coupled to electron transport between dihydrodiphosphopyridine nucleotide and oxygen | journal = The Journal of Biological Chemistry | volume = 178 | issue = 2 | pages = 611–644 | date = April 1949 | pmid = 18116985 | doi = 10.1016/S0021-9258(18)56879-4 | url = http://www.jbc.org/cgi/reprint/178/2/611 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20081216081441/http://www.jbc.org/cgi/reprint/178/2/611 | archive-date = 16 December 2008 }}</ref> The term ''oxidative phosphorylation'' was coined by {{Interlanguage link|Volodymyr Belitser|uk|3=Беліцер Володимир Олександрович}} in 1939.<ref>{{cite journal | vauthors = Kalckar HM | title = 50 years of biological research--from oxidative phosphorylation to energy requiring transport regulation | journal = Annual Review of Biochemistry | volume = 60 | pages = 1–37 | year = 1991 | pmid = 1883194 | doi = 10.1146/annurev.bi.60.070191.000245 | doi-access = free }}</ref><ref>{{Cite journal | vauthors = Belitser VA, Tsibakova ET | title = About phosphorilation mechanism coupled with respiration | journal = [[Biokhimiya]] | volume = 4| pages = 516–534 | year = 1939}}</ref>

For another twenty years, the mechanism by which ATP is generated remained mysterious, with scientists searching for an elusive "high-energy intermediate" that would link oxidation and phosphorylation reactions.<ref>{{cite journal | vauthors = Slater EC | title = Mechanism of phosphorylation in the respiratory chain | journal = Nature | volume = 172 | issue = 4387 | pages = 975–978 | date = November 1953 | pmid = 13111237 | doi = 10.1038/172975a0 | s2cid = 4153659 | bibcode = 1953Natur.172..975S }}</ref> This puzzle was solved by [[Peter D. Mitchell]] with the publication of the [[chemiosmotic theory]] in 1961.<ref>{{cite journal | vauthors = Mitchell P | title = Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism | journal = Nature | volume = 191 | issue = 4784 | pages = 144–148 | date = July 1961 | pmid = 13771349 | doi = 10.1038/191144a0 | s2cid = 1784050 | bibcode = 1961Natur.191..144M }}</ref> At first, this proposal was highly controversial, but it was slowly accepted and Mitchell was awarded a [[Nobel Prize|Nobel prize]] in 1978.<ref>{{cite book |title=Peter Mitchell and the Vital Force | vauthors = Saier Jr MH |oclc = 55202414}}</ref><ref>{{cite web |url=http://nobelprize.org/nobel_prizes/chemistry/laureates/1978/mitchell-lecture.pdf |title=David Keilin's Respiratory Chain Concept and Its Chemiosmotic Consequences |access-date=2007-07-21 | vauthors = Mitchell P |year=1978 |work=Nobel lecture |publisher=Nobel Foundation |url-status=live |archive-url=https://web.archive.org/web/20070927135238/http://nobelprize.org/nobel_prizes/chemistry/laureates/1978/mitchell-lecture.pdf |archive-date=2007-09-27 }}</ref> Subsequent research concentrated on purifying and characterizing the enzymes involved, with major contributions being made by [[David E. Green]] on the complexes of the electron-transport chain, as well as [[Efraim Racker]] on the ATP synthase.<ref>{{cite journal | vauthors = Pullman ME, Penefsky HS, Datta A, Racker E | title = Partial resolution of the enzymes catalyzing oxidative phosphorylation. I. Purification and properties of soluble dinitrophenol-stimulated adenosine triphosphatase | journal = The Journal of Biological Chemistry | volume = 235 | issue = 11 | pages = 3322–3329 | date = November 1960 | pmid = 13738472 | doi = 10.1016/S0021-9258(20)81361-1 | url = http://www.jbc.org/cgi/reprint/235/11/3322 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20070929091858/http://www.jbc.org/cgi/reprint/235/11/3322 | archive-date = 29 September 2007 }}</ref> A critical step towards solving the mechanism of the ATP synthase was provided by [[Paul D. Boyer]], by his development in 1973 of the "binding change" mechanism, followed by his radical proposal of rotational catalysis in 1982.<ref name=Gresser/><ref>{{cite journal | vauthors = Boyer PD, Cross RL, Momsen W | title = A new concept for energy coupling in oxidative phosphorylation based on a molecular explanation of the oxygen exchange reactions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 70 | issue = 10 | pages = 2837–2839 | date = October 1973 | pmid = 4517936 | pmc = 427120 | doi = 10.1073/pnas.70.10.2837 | doi-access = free | bibcode = 1973PNAS...70.2837B }}</ref> More recent work has included [[x-ray crystallography|structural studies]] on the enzymes involved in oxidative phosphorylation by [[John E. Walker]], with Walker and Boyer being awarded a Nobel Prize in 1997.<ref>{{cite web |url=http://nobelprize.org/nobel_prizes/chemistry/laureates/1997/ |title=The Nobel Prize in Chemistry 1997 |access-date=2007-07-21 |publisher=Nobel Foundation |url-status=live |archive-url=https://web.archive.org/web/20170325181904/http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1997/ |archive-date=2017-03-25 }}</ref>