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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s, 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. 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.

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 carbons.

Metabolism

Source and biosynthesis

Valine, like other branched-chain amino acids, is synthesized by bacteria and plants, but not by animals. It is therefore an

essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life forms ...

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 Pyruvic acid (CH3COCOOH) is the simplest of the keto acids, alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate acid, conjugate base, CH3COCOO−, is an metabolic intermediate, intermediate in several m ...

. The initial part of the pathway also leads to leucine. The intermediate α-ketoisovalerate undergoes reductive amination with

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

. Enzymes involved in this biosynthesis include: # Acetolactate synthase (also known as acetohydroxy acid synthase) # Acetohydroxy acid isomeroreductase # Dihydroxyacid dehydratase # Valine aminotransferase

Degradation

Like other branched-chain amino acids, the catabolism of valine starts with the removal of the amino group by

transamination Transamination is a chemical reaction that transfers an amino group to a ketoacid to form new amino acids.This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential a ...

, giving alpha-ketoisovalerate, an alpha- keto acid, which is converted to isobutyryl-CoA 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—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

and provide direct fuel in muscle tissue.

Synthesis

Racemic valine can be synthesized by bromination of isovaleric acid followed by amination of the α-bromo derivative. : :

Medical significance

Metabolic diseases

The degradation of valine is impaired in the following metabolic diseases: * 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. 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. 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. The valine catabolite 3-hydroxyisobutyrate promotes insulin resistance in mice by stimulating fatty acid uptake into muscle and lipid accumulation. In mice, a BCAA-restricted diet decreased fasting blood glucose levels and improved body composition.

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.

References

External links

Valine MS SpectrumValine's relationship to prions
{{Use dmy dates, date=March 2018 Alpha-Amino acids Branched-chain amino acids Proteinogenic amino acids Glucogenic amino acids Essential amino acids Isopropyl compounds Substances discovered in the 1900s