Last updated
Skeletal formula of neutral valine
Valine at 7.4 pH.png
Zwitterionic valine
IUPAC name
Other names
2-Amino-3-methylbutanoic acid
2-Aminoisovaleric acid
Valic acid
3D model (JSmol)
ECHA InfoCard 100.000.703 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • L:200-773-6
PubChem CID
  • InChI=1S/C5H11NO2/c1-3(2)4(6)5(7)8/h3-4H,6H2,1-2H3,(H,7,8)/t4-/m0/s1 Yes check.svgY
  • L:CC(C)[C@@H](C(=O)O)N
  • L Zwitterion:CC(C)[C@@H](C(=O)[O-])[NH3+]
Properties [1]
Molar mass 117.148 g·mol−1
Density 1.316 g/cm3
Melting point 298 °C (568 °F; 571 K) (decomposition)
soluble, 85 g/L [2]
Acidity (pKa)2.32 (carboxyl), 9.62 (amino) [3]
-74.3·10−6 cm3/mol
Supplementary data page
Valine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Valine (symbol Val or V) [4] 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. [5] 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. [6] [7]


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. [8]


Source and biosynthesis

Valine, like other branched-chain amino acids, is synthesized by bacteria and plants, but not by animals. [9] 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. [10] 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: [11]

  1. Acetolactate synthase (also known as acetohydroxy acid synthase)
  2. Acetohydroxy acid isomeroreductase
  3. Dihydroxyacid dehydratase
  4. Valine aminotransferase


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. [12] This is further oxidised and rearranged to succinyl-CoA, which can enter the citric acid cycle.


Racemic valine can be synthesized by bromination of isovaleric acid followed by amination of the α-bromo derivative [13]

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. [14] 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. [15] 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. [16] The valine catabolite 3-hydroxyisobutyrate promotes insulin resistance in mice by stimulating fatty acid uptake into muscle and lipid accumulation. [17] In mice, a BCAA-restricted diet decreased fasting blood glucose levels and improved body composition. [18]

Hematopoietic stem cells

Dietary valine is essential for hematopoietic stem cell (HSC) self-renewal, as demonstrated by experiments in mice. [19] 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

Related Research Articles

<span class="mw-page-title-main">Methionine</span> Sulfur-containing amino acid

Methionine is an essential amino acid in humans.

<span class="mw-page-title-main">Alanine</span> Α-amino acid that is used in the biosynthesis of proteins

Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain. Consequently, its IUPAC systematic name is 2-aminopropanoic acid, and it is classified as a nonpolar, aliphatic α-amino acid. Under biological conditions, it exists in its zwitterionic form with its amine group protonated (as −NH3+) and its carboxyl group deprotonated (as −CO2). It is non-essential to humans as it can be synthesised metabolically and does not need to be present in the diet. It is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG).

<span class="mw-page-title-main">Isoleucine</span> Chemical compound

Isoleucine (symbol Ile or I) 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+3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a hydrocarbon side chain with a branch (a central carbon atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain, aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it. Essential amino acids are necessary in the human diet. In plants isoleucine can be synthesized from threonine and methionine. In plants and bacteria, isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes. It is encoded by the codons AUU, AUC, and AUA.

<span class="mw-page-title-main">Leucine</span> Chemical compound

Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning 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 isobutyl 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, and beans and other legumes. It is encoded by the codons UUA, UUG, CUU, CUC, CUA, and CUG. Leucine is named from λευκός leukós "white" after its common appearance as a white powder, a property it shares with many other amino acids.

<span class="mw-page-title-main">Threonine</span> Amino acid

Threonine is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain containing a hydroxyl group, making it a polar, uncharged amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Threonine is synthesized from aspartate in bacteria such as E. coli. It is encoded by all the codons starting AC.

Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is an ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.

Propionic acidemia, also known as propionic aciduria or propionyl-CoA carboxylase deficiency, is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.

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<span class="mw-page-title-main">Maple syrup urine disease</span> Autosomal recessive metabolic disorder

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness. It was described by John Menkes in the 1950s.

In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride synthesis, with the latter being the process by which fatty acids are esterified to glycerol before being packaged into very-low-density lipoprotein (VLDL). Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triacylglycerol synthesis, on the other hand, occurs in the endoplasmic reticulum membrane of cells by bonding three fatty acid molecules to a glycerol molecule. Both processes take place mainly in liver and adipose tissue. Nevertheless, it also occurs to some extent in other tissues such as the gut and kidney. A review on lipogenesis in the brain was published in 2008 by Lopez and Vidal-Puig. After being packaged into VLDL in the liver, the resulting lipoprotein is then secreted directly into the blood for delivery to peripheral tissues.

<span class="mw-page-title-main">Branched-chain amino acid</span> Amino acid with a branched carbon chain

A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid and alloisoleucine.

<span class="mw-page-title-main">Methylmalonyl-CoA mutase deficiency</span> Medical condition

Methylmalonyl-CoA mutase is a mitochondrial homodimer apoenzyme that focuses on the catalysis of methylmalonyl CoA to succinyl CoA. The enzyme is bound to adenosylcobalamin, a hormonal derivative of vitamin B12 in order to function. Methylmalonyl-CoA mutase deficiency is caused by genetic defect in the MUT gene responsible for encoding the enzyme. Deficiency in this enzyme accounts for 60% of the cases of methylmalonic acidemia.

In chemistry, de novo synthesis is the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as formate and aspartate. Methionine, on the other hand, is needed in the diet because while it can be degraded to and then regenerated from homocysteine, it cannot be synthesized de novo.

<span class="mw-page-title-main">Amino acid synthesis</span> The set of biochemical processes by which amino acids are produced

Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).

In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine to form triglycerides, the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed. Phospholipids form the bulk of the lipid bilayers that make up cell membranes and surrounds the organelles within the cells. In addition to cytosolic fatty acid synthesis, there is also mitochondrial fatty acid synthesis (mtFASII), in which malonyl-CoA is formed from malonic acid with the help of malonyl-CoA synthetase (ACSF3), which then becomes the final product octanoyl-ACP (C8) via further intermediate steps.

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<span class="mw-page-title-main">Ketogenic amino acid</span> Type of amino acid

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Norvaline (abbreviated as Nva) is an amino acid with the formula CH3(CH2)2CH(NH2)CO2H. The compound is a structural analog of valeric acid and also an isomer of the more common amino acid valine. Like most other α-amino acids, norvaline is chiral. It is a white, water-soluble solid.

Combined malonic and methylmalonic aciduria (CMAMMA), also called combined malonic and methylmalonic acidemia is an inherited metabolic disease characterized by elevated levels of malonic acid and methylmalonic acid. Some researchers have hypothesized that CMAMMA might be one of the most common forms of methylmalonic acidemia, and possibly one of the most common inborn errors of metabolism. Due to being infrequently diagnosed, it most often goes undetected.


  1. Weast RC, ed. (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. p. C-569. ISBN   0-8493-0462-8.
  2. "Physicochemical Information". emdmillipore. 2022. Retrieved 17 November 2022.
  3. Dawson RM, Elliott DC, Elliott WH, Jones KM, eds. (1959). Data for Biochemical Research. Oxford: Clarendon Press. ASIN   B000S6TFHA. OCLC   859821178.
  4. "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  5. "Valine". Encyclopædia Britannica Online. Retrieved 6 December 2015.
  6. "Valine". Merriam-Webster Online Dictionary. Retrieved 6 December 2015.
  7. "Valeric acid". Merriam-Webster Online Dictionary. Retrieved 6 December 2015.
  8. Jones JH, ed. (1985). Amino Acids, Peptides and Proteins. Specialist Periodical Reports. Vol. 16. London: Royal Society of Chemistry. p. 389. ISBN   978-0-85186-144-9.
  9. Basuchaudhuri P (2016). Nitrogen metabolism in rice. Boca Raton, Florida: CRC Press. p. 159. ISBN   978-1-4987-4668-7. OCLC   945482059.
  10. 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.
  11. 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..
  12. Mathews CK (2000). Biochemistry. Van Holde, K. E., Ahern, Kevin G. (3rd ed.). San Francisco, Calif.: Benjamin Cummings. p. 776. ISBN   978-0-8053-3066-3. OCLC   42290721.
  13. Marvel CS (1940). "dl-Valine". Organic Syntheses . 20: 106.; Collective Volume, vol. 3, p. 848.
  14. Lynch CJ, Adams SH (December 2014). "Branched-chain amino acids in metabolic signalling and insulin resistance". Nature Reviews. Endocrinology. 10 (12): 723–36. doi:10.1038/nrendo.2014.171. PMC   4424797 . PMID   25287287.
  15. Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, et al. (June 2014). "Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice". Metabolism. 63 (6): 841–50. doi:10.1016/j.metabol.2014.03.006. PMID   24684822.
  16. Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, et al. (February 2018). "Restoration of metabolic health by decreased consumption of branched-chain amino acids". The Journal of Physiology. 596 (4): 623–645. doi:10.1113/JP275075. PMC   5813603 . PMID   29266268.
  17. Jang C, Oh SF, Wada S, Rowe GC, Liu L, Chan MC, et al. (April 2016). "A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance". Nature Medicine. 22 (4): 421–6. doi:10.1038/nm.4057. PMC   4949205 . PMID   26950361.
  18. Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, et al. (July 2016). "Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health". Cell Reports. 16 (2): 520–530. doi:10.1016/j.celrep.2016.05.092. PMC   4947548 . PMID   27346343.
  19. Taya Y, Ota Y, Wilkinson AC, Kanazawa A, Watarai H, Kasai M, et al. (December 2016). "Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation". Science. 354 (6316): 1152–1155. Bibcode:2016Sci...354.1152T. doi:10.1126/science.aag3145. PMID   27934766. S2CID   45815137.