Valine Explained

Valine (symbol Val or V)[1] 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. Valine is essential in humans, meaning the body cannot synthesize it; it must be obtained from dietary sources which are foods that contain proteins, 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.[2] The name valine comes from its structural similarity to valeric acid, which in turn is named after the plant valerian due to the presence of the acid in the roots of the plant.[3] [4]

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.[5]

Metabolism

Source and biosynthesis

Valine, like other branched-chain amino acids, is synthesized by bacteria and plants, but not by animals.[6] It is therefore an essential amino acid in animals, and needs to be present in the diet. Adult humans require about 24 mg/kg body weight daily.[7] 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:[8]

  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.[9] 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[10]

HO2CCH2CH(CH3)2 + Br2 → HO2CCHBrCH(CH3)2 + HBr

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

Medical significance

Metabolic diseases

The degradation of valine is impaired in the following metabolic diseases:

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.[11] 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.[12] 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.[13] The valine catabolite 3-hydroxyisobutyrate promotes insulin resistance in mice by stimulating fatty acid uptake into muscle and lipid accumulation.[14] In mice, a BCAA-restricted diet decreased fasting blood glucose levels and improved body composition.[15]

Hematopoietic stem cells

Dietary valine is essential for hematopoietic stem cell (HSC) self-renewal, as demonstrated by experiments in mice.[16] 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

External links

Notes and References

  1. Web site: Nomenclature and Symbolism for Amino Acids and Peptides . IUPAC-IUB Joint Commission on Biochemical Nomenclature . 1983 . 5 March 2018. https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html. 9 October 2008 . live.
  2. Encyclopedia: Valine . Encyclopædia Britannica Online . 2015-12-06.
  3. Web site: Valine . Merriam-Webster Online Dictionary . 2015-12-06.
  4. Web site: Valeric acid . Merriam-Webster Online Dictionary . 2015-12-06.
  5. Book: Jones JH . Amino Acids, Peptides and Proteins . . Specialist Periodical Reports . 16 . London . 1985 . 389 . 978-0-85186-144-9 .
  6. Book: Nitrogen metabolism in rice. Basuchaudhuri P . CRC Press. 2016. 978-1-4987-4668-7 . Boca Raton, Florida. 159. 945482059.
  7. Book: Institute of Medicine . Institute of Medicine . Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids . Protein and Amino Acids . The National Academies Press . 2002 . Washington, DC . 589–768 . https://www.nap.edu/read/10490/chapter/12 . 10.17226/10490 . 978-0-309-08537-3 .
  8. .
  9. Book: Biochemistry. Mathews CK . 2000. Benjamin Cummings. Van Holde, K. E., Ahern, Kevin G.. 978-0-8053-3066-3 . 3rd. San Francisco, Calif.. 776. 42290721.
  10. .
  11. Lynch CJ, Adams SH . Branched-chain amino acids in metabolic signalling and insulin resistance . Nature Reviews. Endocrinology . 10 . 12 . 723–36 . December 2014 . 25287287 . 4424797 . 10.1038/nrendo.2014.171 .
  12. Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, Chen S, Zhu J, Sheng H, Guo F . 6 . Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice . Metabolism . 63 . 6 . 841–50 . June 2014 . 24684822 . 10.1016/j.metabol.2014.03.006 .
  13. 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 . 6 . Restoration of metabolic health by decreased consumption of branched-chain amino acids . The Journal of Physiology . 596 . 4 . 623–645 . February 2018 . 29266268 . 5813603 . 10.1113/JP275075 .
  14. 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 . 6 . A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance . Nature Medicine . 22 . 4 . 421–6 . April 2016 . 26950361 . 4949205 . 10.1038/nm.4057 .
  15. 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 . 6 . Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health . Cell Reports . 16 . 2 . 520–530 . July 2016 . 27346343 . 4947548 . 10.1016/j.celrep.2016.05.092 .
  16. Taya Y, Ota Y, Wilkinson AC, Kanazawa A, Watarai H, Kasai M, Nakauchi H, Yamazaki S . 6 . Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation . Science . 354 . 6316 . 1152–1155 . December 2016 . 27934766 . 10.1126/science.aag3145 . 45815137 . 2016Sci...354.1152T .

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