Editing Valine

{{chembox
| Name           = Valine
| ImageFileL1    = L-valine-2D-skeletal.png
| ImageCaptionL1 = [[Skeletal formula]] of neutral valine
| ImageClassL1   = skin-invert-image
| ImageFileR1    = Valine at 7.4 pH.png
| ImageCaptionR1 = [[Zwitterionic]] valine
| ImageFileL2    = Valine-from-xtal-3D-bs-17.png
| ImageSizeL2    = 
| ImageCaptionL2 = [[Ball-and-stick model]]
| ImageFileR2    = Valine-from-xtal-3D-sf.png
| ImageSizeR2    = 
| ImageCaptionR2 = [[Space-filling model]]
| IUPACName      = Valine
| OtherNames     = 2-Aminoisovaleric acid<br/>Valic acid
| SystematicName = 2-Amino-3-methylbutanoic acid
| Section1       = {{Chembox Identifiers
| index1_label = D/L
| index2_label = D
| index_label = L <!-- needs to be L valine (natural isomer) so drugbank etc. take correct index_label -->
| IUPHAR_ligand = 4794
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6050
| ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1 =1148
| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID2 =64635
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII1 = 4CA13A832H
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = HG18B9YRS7
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = Y14I1443UR
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 43068
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00039
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H11NO2/c1-3(2)4(6)5(7)8/h3-4H,6H2,1-2H3,(H,7,8)/t4-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KZSNJWFQEVHDMF-BYPYZUCNSA-N
| InChIKey1 = KZSNJWFQEVHDMF-UHFFFAOYSA-N
| InChIKey2 = KZSNJWFQEVHDMF-SCSAIBSYSA-N
| CASNo1 = 516-06-3
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo =72-18-4
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo2 = 640-68-6
| CASNo2_Ref = {{cascite|correct|CAS}}
| EC_number = 200-773-6 <!-- 208-220-0 (DL-isomer), 211-368-9 (D-isomer) but Chembox can only have one -->
| PubChem = 6287
| PubChem1 = 1182
| PubChem2 = 71563
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00161
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16414
| SMILES = CC(C)[C@@H](C(=O)O)N
| SMILES3 = CC(C)[C@@H](C(=O)[O-])[NH3+]
| SMILES3_Comment = L [[Zwitterion]]
}}
| Section2       = {{Chembox Properties
| Properties_ref = <ref>{{RubberBible62nd|page=C-569|name-list-style = vanc }}</ref>
| C=5 | H=11 | N=1 | O=2
| Appearance =
| Density = 1.316 g/cm<sup>3</sup>
| MeltingPtC = 298
| MeltingPt_notes = (decomposition)
| Solubility = soluble, 85 g/L <ref>{{cite web| url = https://www.emdmillipore.com/US/en/product/S-Valine,MDA_CHEM-816006 | title = Physicochemical Information | publisher = emdmillipore | year = 2022 | access-date = 17 November 2022}}</ref>
| pKa =2.32 (carboxyl), 9.62 (amino)<ref>{{cite book | veditors =  Dawson RM, Elliott DC, Elliott WH, Jones KM | title = Data for Biochemical Research | location = Oxford | publisher = Clarendon Press | date = 1959 | asin = B000S6TFHA | oclc = 859821178 }}</ref>
| MagSus = −74.3·10<sup>−6</sup> cm<sup>3</sup>/mol
  }}
| Section7       = {{Chembox Hazards
| FlashPt =
 }}
}}
[[File:Valine-spin.gif|thumb|Valine ball and stick model spinning]]
'''Valine''' (symbol '''Val''' or '''V''')<ref>{{cite web| url = http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | title = Nomenclature and Symbolism for Amino Acids and Peptides | publisher = IUPAC-IUB Joint Commission on Biochemical Nomenclature | year = 1983 | access-date = 5 March 2018| archive-url= https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html| archive-date= 9 October 2008 | url-status= live}}</ref> is an α-[[amino acid]] that is used in the biosynthesis of proteins. It contains an α-[[amino group]] (which is in the protonated −NH<sub>3</sub><sup>+</sup> form under biological conditions), an α-[[Carboxylic acid|carboxylic acid group]] (which is in the deprotonated −COO<sup>−</sup> form under biological conditions), and a side chain [[Isopropyl|isopropyl group]], making it a [[Chemical polarity|non-polar]] [[Aliphatic compound|aliphatic]] amino acid. Valine is [[Essential amino acid|essential]] in humans, meaning the body cannot synthesize it; it must be obtained from dietary sources which are foods that contain [[protein]]s, such as meats, dairy products, soy products, beans and legumes. It is [[Genetic code|encoded]] by all [[codons]] starting with GU (GUU, GUC, GUA, and GUG).

==History and etymology==
Valine was first isolated from [[casein]] in 1901 by [[Hermann Emil Fischer]].<ref>{{cite encyclopedia |url=http://www.britannica.com/EBchecked/topic/622178/valine |title=Valine |encyclopedia=Encyclopædia Britannica Online |access-date=2015-12-06}}</ref> The name valine comes from its structural similarity to [[valeric acid]], which in turn is named after the plant [[Valerian (herb)|valerian]] due to the presence of the acid in the roots of the plant.<ref>{{cite web |url=http://www.merriam-webster.com/dictionary/valine |title=Valine |work=Merriam-Webster Online Dictionary |access-date=2015-12-06}}</ref><ref>{{cite web |url=http://www.merriam-webster.com/dictionary/valeric+acid |title=Valeric acid |work=Merriam-Webster Online Dictionary |access-date=2015-12-06}}</ref>

==Nomenclature==
According to [[IUPAC nomenclature of organic chemistry|IUPAC]], carbon atoms forming valine are numbered sequentially starting from 1 denoting the [[Carboxylic acid|carboxyl]] carbon, whereas 4 and 4' denote the two terminal [[Methyl group|methyl]] carbons.<ref>{{cite book | veditors = Jones JH | title = Amino Acids, Peptides and Proteins | publisher = [[Royal Society of Chemistry]] | series = Specialist Periodical Reports | volume = 16 | location = London | date = 1985 | page = 389 | isbn = 978-0-85186-144-9 }}</ref>

==Metabolism==
===Source and biosynthesis===
Valine, like other branched-chain amino acids, is synthesized by bacteria and plants, but not by animals.<ref>{{Cite book|url=https://books.google.com/books?id=shDYCwAAQBAJ&pg=PA159|title=Nitrogen metabolism in rice| vauthors = Basuchaudhuri P |publisher=CRC Press|year=2016|isbn=978-1-4987-4668-7 |location=Boca Raton, Florida|pages=159|oclc=945482059}}</ref> It is therefore an [[essential amino acid]] in animals, and needs to be present in the diet. Adult humans require about 24&nbsp;mg/kg body weight daily.<ref name="DRItext">{{cite book | last1 = Institute of Medicine | author-link = Institute of Medicine | title = Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids | chapter = Protein and Amino Acids | publisher = The National Academies Press | year = 2002 | location = Washington, DC | pages = 589–768 | chapter-url = https://www.nap.edu/read/10490/chapter/12 | doi = 10.17226/10490 | isbn = 978-0-309-08537-3 }}</ref> It is synthesized in plants and bacteria via several steps starting from [[pyruvic acid]]. The initial part of the pathway also leads to [[leucine]]. The intermediate [[alpha-Ketoisovaleric acid|α-ketoisovalerate]] undergoes [[reductive amination]] with [[glutamate]].  Enzymes involved in this biosynthesis include:<ref>{{Lehninger3rd}}.</ref>
# [[Acetolactate synthase]] (also known as acetohydroxy acid synthase)
# [[Ketol-acid reductoisomerase|Acetohydroxy acid isomeroreductase]]
# [[Dihydroxyacid dehydratase]]
# [[Valine—pyruvate transaminase|Valine aminotransferase]]

=== Degradation ===
Like other branched-chain amino acids, the catabolism of valine starts with the removal of the amino group by [[transamination]], giving [[Alpha-Ketoisovaleric acid|alpha-ketoisovalerate]], an alpha-[[keto acid]], which is converted to [[isobutyryl-CoA]] through [[oxidative decarboxylation]] by the [[Branched-chain alpha-keto acid dehydrogenase complex|branched-chain α-ketoacid dehydrogenase complex]].<ref name=":0">{{Cite book|title=Biochemistry| vauthors = Mathews CK |date=2000|publisher=Benjamin Cummings|others=Van Holde, K. E., Ahern, Kevin G.|isbn=978-0-8053-3066-3 |edition=3rd|location=San Francisco, Calif.|pages=776|oclc=42290721}}</ref> This is further oxidised and rearranged to [[succinyl-CoA]], which can enter the [[citric acid cycle]] and provide direct fuel in muscle tissue.<ref>{{cite web |url=https://www.stanfordchem.com/l-valine.html |title=L-Valine |website=Stanford Chemicals |access-date=Oct 29, 2024}}</ref><ref>{{cite book |last=Kumari |first=Asha |year=2023 |title=Sweet Biochemistry |edition=5th |pages=9–15 |chapter=Chapter 2 - Citric acid cycle |publisher=Academic Press |isbn=9780443153488}}</ref>

==Synthesis==
[[Racemic]] valine can be synthesized by bromination of [[3-Methylbutanoic acid|isovaleric acid]] followed by amination of the α-bromo derivative.<ref>{{OrgSynth | vauthors = Marvel CS | title = ''dl''-Valine | prep = CV3P0848 | volume = 20 | page = 106 | year = 1940 | collvol = 3 | collvolpages = 848}}.</ref>
:HO<sub>2</sub>CCH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub>  + [[Bromine|Br<sub>2</sub>]]   →    HO<sub>2</sub>CCHBrCH(CH<sub>3</sub>)<sub>2</sub>  + [[hydrogen bromide|HBr]]
:HO<sub>2</sub>CCHBrCH(CH<sub>3</sub>)<sub>2</sub>  +  2 NH<sub>3</sub>   →    HO<sub>2</sub>CCH(NH<sub>2</sub>)CH(CH<sub>3</sub>)<sub>2</sub>  +  NH<sub>4</sub>Br

== Medical significance ==

=== Metabolic diseases ===
The degradation of valine is impaired in the following [[Metabolic disorder|metabolic diseases]]:{{cn|date=October 2024}}

* [[Combined malonic and methylmalonic aciduria]] (CMAMMA)
* [[Maple syrup urine disease]] (MSUD)
* [[Methylmalonic acidemia]]
* [[Propionic acidemia]]

=== Insulin resistance ===
Lower levels of serum valine, like other branched-chain amino acids, are associated with weight loss and decreased [[insulin resistance]]: higher levels of valine are observed in the blood of diabetic mice, rats, and humans.<ref>{{cite journal | vauthors = Lynch CJ, Adams SH | title = Branched-chain amino acids in metabolic signalling and insulin resistance | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 12 | pages = 723–36 | date = December 2014 | pmid = 25287287 | pmc = 4424797 | doi = 10.1038/nrendo.2014.171 }}</ref> Mice fed a BCAA-deprived diet for one day had improved insulin sensitivity, and feeding of a valine-deprived diet for one week significantly decreases blood glucose levels.<ref>{{cite journal | vauthors = Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, Chen S, Zhu J, Sheng H, Guo F | display-authors = 6 | title = Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice | journal = Metabolism | volume = 63 | issue = 6 | pages = 841–50 | date = June 2014 | pmid = 24684822 | doi = 10.1016/j.metabol.2014.03.006 }}</ref> In diet-induced obese and insulin resistant mice, a diet with decreased levels of valine and the other branched-chain amino acids resulted in a rapid reversal of the adiposity and an improvement in glucose-level control.<ref>{{cite journal | vauthors = Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW | display-authors = 6 | title = Restoration of metabolic health by decreased consumption of branched-chain amino acids | journal = The Journal of Physiology | volume = 596 | issue = 4 | pages = 623–645 | date = February 2018 | pmid = 29266268 | pmc = 5813603 | doi = 10.1113/JP275075 }}</ref> The valine catabolite [[3-Hydroxyisobutyric acid|3-hydroxyisobutyrate]] promotes insulin resistance in mice by stimulating fatty acid uptake into muscle and lipid accumulation.<ref>{{cite journal | vauthors = Jang C, Oh SF, Wada S, Rowe GC, Liu L, Chan MC, Rhee J, Hoshino A, Kim B, Ibrahim A, Baca LG, Kim E, Ghosh CC, Parikh SM, Jiang A, Chu Q, Forman DE, Lecker SH, Krishnaiah S, Rabinowitz JD, Weljie AM, Baur JA, Kasper DL, Arany Z | display-authors = 6 | title = A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance | journal = Nature Medicine | volume = 22 | issue = 4 | pages = 421–6 | date = April 2016 | pmid = 26950361 | pmc = 4949205 | doi = 10.1038/nm.4057 }}</ref> In mice, a BCAA-restricted diet decreased fasting blood glucose levels and improved body composition.<ref>{{cite journal | vauthors = Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW | display-authors = 6 | title = Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health | journal = Cell Reports | volume = 16 | issue = 2 | pages = 520–530 | date = July 2016 | pmid = 27346343 | pmc = 4947548 | doi = 10.1016/j.celrep.2016.05.092 }}</ref>

=== Hematopoietic stem cells ===
Dietary valine is essential for [[hematopoietic stem cell]] (HSC) self-renewal, as demonstrated by experiments in mice.<ref>{{cite journal | vauthors = Taya Y, Ota Y, Wilkinson AC, Kanazawa A, Watarai H, Kasai M, Nakauchi H, Yamazaki S | display-authors = 6 | title = Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation | journal = Science | volume = 354 | issue = 6316 | pages = 1152–1155 | date = December 2016 | pmid = 27934766 | doi = 10.1126/science.aag3145 | s2cid = 45815137 | bibcode = 2016Sci...354.1152T }}</ref> Dietary valine restriction selectively depletes long-term repopulating HSC in mouse bone marrow. Successful stem cell transplantation was achieved in mice without irradiation after 3 weeks on a valine restricted diet. Long-term survival of the transplanted mice was achieved when valine was returned to the diet gradually over a 2-week period to avoid [[refeeding syndrome]].

== See also ==
* [[Valinol]]

== References ==
{{Reflist}}

== External links ==
* [http://gmd.mpimp-golm.mpg.de/Spectrums/c5dd47e7-96b1-4dd1-b079-4490774c199d.aspx Valine MS Spectrum]
*[http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/IleVal.html Isoleucine and valine biosynthesis]
*[https://www.washingtonpost.com/news/morning-mix/wp/2015/06/11/how-a-history-of-eating-human-brains-protected-this-tribe-from-brain-disease/?tid=hp_mm Valine's relationship to prions]

{{Amino acids}}
{{Amino acid metabolism intermediates}}
{{Use dmy dates|date=March 2018}}

[[Category:Alpha-Amino acids]]
[[Category:Branched-chain amino acids]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Essential amino acids]]
[[Category:Isopropyl compounds]]
[[Category:Substances discovered in the 1900s]]