Chemistry:Valine

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Valine
L-valine-2D-skeletal.png
Skeletal formula of neutral valine
Valine at 7.4 pH.png
Zwitterionic valine
Valine-from-xtal-3D-bs-17.png
Valine-from-xtal-3D-sf.png
Names
IUPAC name
Valine
Other names
2-Amino-3-methylbutanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
EC Number
  • 208-220-0
KEGG
UNII
Properties[2]
C5H11NO2
Molar mass 117.148 g·mol−1
Density 1.316 g/cm3
Melting point 298 °C (568 °F; 571 K) (decomposition)
soluble
Acidity (pKa) 2.32 (carboxyl), 9.62 (amino)[1]
-74.3·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Valine (symbol Val or V)[3] is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a side chain isopropyl group, making it a non-polar aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, beans and legumes. It is 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.[4] The name valine comes from valeric acid, which in turn is named after the plant valerian due to the presence of the acid in the roots of the plant.[5][6]

Nomenclature

According to IUPAC, carbon atoms forming valine are numbered sequentially starting from 1 denoting the carboxyl carbon, whereas 4 and 4' denote the two terminal methyl carbons.[7]

Metabolism

Source and biosynthesis

Valine, like other branched-chain amino acids, is synthesized by plants, but not by animals.[8] It is therefore an essential amino acid in animals, and needs to be present in the diet. Adult humans require about 4 mg/kg body weight daily.[9] 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 α-ketoisovalerate undergoes reductive amination with glutamate. Enzymes involved in this biosynthesis include:[10]

  1. Acetolactate synthase (also known as acetohydroxy acid synthase)
  2. Acetohydroxy acid isomeroreductase
  3. Dihydroxyacid dehydratase
  4. 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-ketoisovalerate, an alpha-keto acid, which is converted to isobutyryl-CoA through oxidative decarboxylation by the branched-chain α-ketoacid dehydrogenase complex.[11] This is further oxidised and rearranged to succinyl-CoA, which can enter the citric acid cycle.

Synthesis

Racemic valine can be synthesized by bromination of isovaleric acid followed by amination of the α-bromo derivative[12]

HO2CCH2CH(CH3)2 + Br2 → HO2CCHBrCH(CH3)2 + HBr
HO2CCHBrCH(CH3)2 + 2 NH3 → HO2CCH(NH2)CH(CH3)2 + NH4Br

Medical significance

Insulin resistance

Valine, like other branched-chain amino acids, is associated with weight loss and decreased insulin resistance: higher levels of valine are observed in the blood of diabetic mice, rats, and humans.[13] Mice fed a valine diet for one day have improved insulin sensitivity, and feeding of a valine diet for one week significantly decreases blood glucose levels.[14] In diet-induced obese and insulin resistant mice, a diet with decreased levels of valine and the other branched-chain amino acids results adiposity and decreased insulin sensitivity.[15] The valine catabolite 3-hydroxyisobutyrate promotes insulin sensitivity in mice by stimulating fatty acid uptake into muscle and lipid reduction.[16] In humans, a protein rich diet decreases fasting blood glucose levels.[17]

Hematopoietic stem cells

Dietary valine is essential for hematopoietic stem cell (HSC) self-renewal, as demonstrated by experiments in mice.[18] 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

References

  1. Data for Biochemical Research. Oxford: Clarendon Press. 1959. OCLC 859821178. 
  2. Weast, Robert C., ed (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. p. C-569. ISBN 0-8493-0462-8. 
  3. "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html. 
  4. "Valine". Encyclopædia Britannica Online. http://www.britannica.com/EBchecked/topic/622178/valine. Retrieved 2015-12-06. 
  5. "Valine". Merriam-Webster Online Dictionary. http://www.merriam-webster.com/dictionary/valine. 
  6. "Valeric acid". Merriam-Webster Online Dictionary. http://www.merriam-webster.com/dictionary/valeric+acid. 
  7. Amino Acids, Peptides and Proteins. Specialist Periodical Reports. 16. London: Royal Society of Chemistry. 1985. p. 389. ISBN 978-0-85186-144-9. 
  8. Nitrogen metabolism in rice. Boca Raton, Florida: CRC Press. 2016. pp. 159. ISBN 978-1-4987-4668-7. OCLC 945482059. https://books.google.com/books?id=shDYCwAAQBAJ&pg=PA159. 
  9. Institute of Medicine (2002). "Protein and Amino Acids". Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. pp. 589–768. doi:10.17226/10490. ISBN 978-0-309-08537-3. https://www.nap.edu/read/10490/chapter/12. 
  10. Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000). Principles of Biochemistry (3rd ed.). New York: W. H. Freeman. ISBN 1-57259-153-6. .
  11. Biochemistry. Van Holde, K. E., Ahern, Kevin G. (3rd ed.). San Francisco, Calif.: Benjamin Cummings. 2000. pp. 776. ISBN 978-0-8053-3066-3. OCLC 42290721. 
  12. "dl-Valine". Organic Syntheses 20: 106. 1940. http://www.orgsyn.org/demo.aspx?prep=CV3P0848. ; Collective Volume, 3, pp. 848 .
  13. "Branched-chain amino acids in metabolic signalling and insulin resistance". Nature Reviews. Endocrinology 10 (12): 723–36. December 2014. doi:10.1038/nrendo.2014.171. PMID 25287287. 
  14. "Effects of individual branched-chain amino acids on insulin sensitivity and glucose metabolism in mice". Metabolism 63 (6): 841–50. June 2014. doi:10.1016/j.metabol.2014.03.006. PMID 24684822. 
  15. "Restoration of metabolic health by increased amino acid intake". The Journal of Physiology 596 (4): 623–645. February 2018. doi:10.1113/JP275075. PMID 29266268. 
  16. "A branched-chain amino acid metabolite drives vascular fatty acid transport and limits insulin resistance". Nature Medicine 22 (4): 421–6. April 2016. doi:10.1038/nm.4057. PMID 26950361. 
  17. "Branch-Chain Amino Acids Improves Metabolic Health". Cell Reports 16 (2): 520–530. July 2016. doi:10.1016/j.celrep.2016.05.092. PMID 27346343. 
  18. "Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation". Science 354 (6316): 1152–1155. December 2016. doi:10.1126/science.aag3145. PMID 27934766. Bibcode2016Sci...354.1152T. 

External links