Editing Transferase (section)

==History==
Some of the most important discoveries relating to transferases occurred as early as the 1930s.  Earliest discoveries of transferase activity occurred in other classifications of [[enzyme]]s, including [[beta-galactosidase]], [[protease]], and acid/base [[phosphatase]].  Prior to the realization that individual enzymes were capable of such a task, it was believed that two or more enzymes enacted functional group transfers.<ref name="pmid13072573">{{cite journal | vauthors = Morton RK | title = Transferase activity of hydrolytic enzymes | journal = Nature | volume = 172 | issue = 4367 | pages = 65–8 | date = Jul 1953 | pmid = 13072573 | doi = 10.1038/172065a0 | bibcode = 1953Natur.172...65M | s2cid = 4180213 }}</ref>
[[Image:Dopamine degradation.svg|thumb|right|Biodegradation of dopamine via catechol-O-methyltransferase (along with other enzymes). The mechanism for dopamine degradation led to the Nobel Prize in Physiology or Medicine in 1970.]]

[[Transamination]], or the transfer of an [[amine]] (or NH<sub>2</sub>) group from an amino acid to a [[keto acid]] by an [[aminotransferase]] (also known as a "transaminase"), was first noted in 1930 by [[Dorothy M. Needham]], after observing the disappearance of [[glutamic acid]] added to pigeon breast muscle.<ref>{{cite journal |last1=Needham |first1=Dorothy M |title=A quantitative study of succinic acid in muscle: Glutamic and aspartic acids as precursors. |journal=Biochem J |date=1930 |volume=24 |issue=1 |pages=208–27 |doi=10.1042/bj0240208 |pmid=16744345 |pmc=1254374}}</ref> This observance was later verified by the discovery of its reaction mechanism by Braunstein and Kritzmann in 1937.<ref>{{cite journal | vauthors = Snell EE, Jenkins WT | title = The mechanism of the transamination reaction|journal=Journal of Cellular and Comparative Physiology |date=December 1959 | volume = 54 | issue = S1 | pages = 161–177 | doi = 10.1002/jcp.1030540413 | pmid = 13832270}}</ref>  Their analysis showed that this reversible reaction could be applied to other tissues.<ref>{{cite journal | vauthors = Braunstein AE, Kritzmann MG | title = Formation and Breakdown of Amino-acids by Inter-molecular Transfer of the Amino Group | journal = Nature | year = 1937 | volume = 140 | issue = 3542 | pages = 503–504 | doi = 10.1038/140503b0 | bibcode = 1937Natur.140R.503B | s2cid = 4009655 }}</ref>   This assertion was validated by [[Rudolf Schoenheimer]]'s work with [[radioisotope]]s as [[Isotopic labelling|tracers]] in 1937.<ref>{{cite book|last=Schoenheimer|first=Rudolf | name-list-style = vanc | title = The Dynamic State of Body Constituents | year = 1949 | publisher = Hafner Publishing Co Ltd | isbn = 978-0-02-851800-8 }}</ref><ref name="pmid1941176">{{cite journal | vauthors = Guggenheim KY | title = Rudolf Schoenheimer and the concept of the dynamic state of body constituents | journal = The Journal of Nutrition | volume = 121 | issue = 11 | pages = 1701–4 | date = Nov 1991 | pmid = 1941176 | doi =  10.1093/jn/121.11.1701| doi-access = free }}</ref> This in turn would pave the way for the possibility that similar transfers were a primary means of producing most amino acids via amino transfer.<ref name="pmid14780123">{{cite journal | vauthors = Hird FJ, Rowsell EV | title = Additional transaminations by insoluble particle preparations of rat liver | journal = Nature | volume = 166 | issue = 4221 | pages = 517–8 | date = Sep 1950 | pmid = 14780123 | doi = 10.1038/166517a0 | bibcode = 1950Natur.166..517H | s2cid = 4215187 }}</ref>

Another such example of early transferase research and later reclassification involved the discovery of uridyl transferase.  In 1953, the enzyme [[UDP-glucose pyrophosphorylase]] was shown to be a transferase, when it was found that it could reversibly produce [[uridine triphosphate|UTP]] and [[glucose 1-phosphate|G1P]] from [[Uridine diphosphate glucose|UDP-glucose]] and an organic [[pyrophosphate]].<ref name="pmid13111246">{{cite journal | vauthors = Munch-Petersen A, Kalckar HM, Cutolo E, Smith EE | title = Uridyl transferases and the formation of uridine triphosphate; enzymic production of uridine triphosphate: uridine diphosphoglucose pyrophosphorolysis | journal = Nature | volume = 172 | issue = 4388 | pages = 1036–7 | date = Dec 1953 | pmid = 13111246 | doi = 10.1038/1721036a0 | bibcode = 1953Natur.172.1036M | s2cid = 452922 }}</ref>

Another example of historical significance relating to transferase is the discovery of the mechanism of [[catecholamine]] breakdown by [[catechol-O-methyltransferase]].  This discovery was a large part of the reason for [[Julius Axelrod]]’s 1970 [[Nobel Prize in Physiology or Medicine]] (shared with [[Bernard Katz|Sir Bernard Katz]] and [[Ulf von Euler]]).<ref>{{cite web|title=Physiology or Medicine 1970 - Press Release|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1970/press.html|work=Nobelprize.org|publisher=Nobel Media AB|access-date=5 November 2013}}</ref>

Classification of transferases continues to this day, with new ones being discovered frequently.<ref>{{cite journal | vauthors = Lambalot RH, Gehring AM, Flugel RS, Zuber P, LaCelle M, Marahiel MA, Reid R, Khosla C, Walsh CT | title = A new enzyme superfamily - the phosphopantetheinyl transferases | journal = Chemistry & Biology | volume = 3 | issue = 11 | pages = 923–36 | date = Nov 1996 | pmid = 8939709 | doi = 10.1016/S1074-5521(96)90181-7 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wongtrakul J, Pongjaroenkit S, Leelapat P, Nachaiwieng W, Prapanthadara LA, Ketterman AJ | title = Expression and characterization of three new glutathione transferases, an epsilon (AcGSTE2-2), omega (AcGSTO1-1), and theta (AcGSTT1-1) from Anopheles cracens (Diptera: Culicidae), a major Thai malaria vector | journal = Journal of Medical Entomology | volume = 47 | issue = 2 | pages = 162–71 | date = Mar 2010 | pmid = 20380296 | doi = 10.1603/me09132 | s2cid = 23558834 }}</ref>  An example of this is Pipe, a sulfotransferase involved in the dorsal-ventral patterning of ''[[Drosophila]]''.<ref>{{cite journal | vauthors = Sen J, Goltz JS, Stevens L, Stein D | title = Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal-ventral polarity | journal = Cell | volume = 95 | issue = 4 | pages = 471–81 | date = Nov 1998 | pmid = 9827800 | doi = 10.1016/s0092-8674(00)81615-3 | s2cid = 27722532 | doi-access = free }}</ref>  Initially, the exact mechanism of Pipe was unknown, due to a lack of information on its substrate.<ref>{{cite journal | vauthors = Moussian B, Roth S | title = Dorsoventral axis formation in the Drosophila embryo--shaping and transducing a morphogen gradient | journal = Current Biology | volume = 15 | issue = 21 | pages = R887–99 | date = Nov 2005 | pmid = 16271864 | doi = 10.1016/j.cub.2005.10.026 | s2cid = 15984116 | doi-access = free | bibcode = 2005CBio...15.R887M }}</ref>  Research into Pipe's catalytic activity eliminated the likelihood of it being a heparan sulfate [[glycosaminoglycan]].<ref>{{cite journal | vauthors = Zhu X, Sen J, Stevens L, Goltz JS, Stein D | title = Drosophila pipe protein activity in the ovary and the embryonic salivary gland does not require heparan sulfate glycosaminoglycans | journal = Development | volume = 132 | issue = 17 | pages = 3813–22 | date = Sep 2005 | pmid = 16049108 | doi = 10.1242/dev.01962 | doi-access = free }}</ref>  Further research has shown that Pipe targets the ovarian structures for sulfation.<ref>{{cite journal | vauthors = Zhang Z, Stevens LM, Stein D | title = Sulfation of eggshell components by Pipe defines dorsal-ventral polarity in the Drosophila embryo | journal = Current Biology | volume = 19 | issue = 14 | pages = 1200–5 | date = Jul 2009 | pmid = 19540119 | doi = 10.1016/j.cub.2009.05.050 | pmc=2733793| bibcode = 2009CBio...19.1200Z }}</ref> Pipe is currently classified as a ''Drosophila'' [[heparan sulfate 2-O-sulfotransferase]].<ref>{{cite journal | vauthors = Xu D, Song D, Pedersen LC, Liu J | title = Mutational study of heparan sulfate 2-O-sulfotransferase and chondroitin sulfate 2-O-sulfotransferase | journal = The Journal of Biological Chemistry | volume = 282 | issue = 11 | pages = 8356–67 | date = Mar 2007 | pmid = 17227754 | doi = 10.1074/jbc.M608062200 | doi-access = free }}</ref>