Valine (symbol Val or V) is an α-
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
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 side chain
isopropyl group, making it a
non-polar aliphatic
In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane ...
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
Casein ( , from Latin ''caseus'' "cheese") is a family of related phosphoproteins ( αS1, aS2, β, κ) that are commonly found in mammalian milk, comprising about 80% of the proteins in cow's milk and between 20% and 60% of the proteins in hum ...
in 1901 by
Hermann Emil Fischer
Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of draw ...
. 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.
Nomenclature
According to
IUPAC
The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
, carbon atoms forming valine are numbered sequentially starting from 1 denoting the
carboxyl carbon, whereas 4 and 4' denote the two terminal
methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...
carbons.
Metabolism
Source and biosynthesis
Valine, like other branched-chain amino acids, is synthesized by plants, but not by animals. 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.
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:
#
Acetolactate synthase (also known as acetohydroxy acid synthase)
#
Acetohydroxy acid isomeroreductase
#
Dihydroxyacid dehydratase
The enzyme dihydroxy-acid dehydratase () catalyzes the chemical reaction
:2,3-dihydroxy-3-methylbutanoate \rightleftharpoons 3-methyl-2-oxobutanoate + H2O
This enzyme participates in valine, leucine and isoleucine biosynthesis and pantothenate ...
# 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
Isobutyryl-coenzyme A is a starting material for many natural products derived from Poly-Ketide Synthase (PKS) assembly lines, as well as PKS-NRPS hybrid assembly lines. These products can often be used as antibiotics. Notably, it is also an interm ...
through
oxidative decarboxylation by the
branched-chain α-ketoacid dehydrogenase complex.
This is further oxidised and rearranged to
succinyl-CoA, which can enter the
citric acid cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prot ...
.
Synthesis
Racemic valine can be synthesized by bromination of
isovaleric acid followed by amination of the α-bromo derivative
:HO
2CCH
2CH(CH
3)
2 +
Br2 → HO
2CCHBrCH(CH
3)
2 +
HBr
:HO
2CCHBrCH(CH
3)
2 + 2 NH
3 → HO
2CCH(NH
2)CH(CH
3)
2 + NH
4Br
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. 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. In diet-induced obese and insulin resistant mice, a diet with decreased levels of valine and the other branched-chain amino acids results in a rapid reversal of the adiposity and an improvement in glucose-level control. The valine catabolite
3-hydroxyisobutyrate promotes insulin sensitivity in mice by stimulating fatty acid uptake into muscle and lipid reduction. In humans, a protein rich diet decreases fasting blood glucose levels.
Hematopoietic stem cells
Dietary valine is essential for
hematopoietic stem cell (HSC) self-renewal, as demonstrated by experiments in mice.
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
Valinol is an organic compound named after, and commonly produced from, the amino acid valine. The compound is chiral and is produced almost exclusively as the S‑isomer (also designated as the L‑isomer), due to the abundant supply of S-valine. ...
References
External links
Valine MS SpectrumValine's relationship to prions
{{Use dmy dates, date=March 2018
Branched-chain amino acids
Proteinogenic amino acids
Glucogenic amino acids
Essential amino acids
Isopropyl compounds
Substances discovered in the 1900s