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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).

Like leucine and isoleucine, valine is a branched-chain amino acid. In sickle-cell disease, a single glutamic acid in β-globin is replaced with valine. Because valine is hydrophobic, whereas glutamic acid is hydrophilic, this change makes the hemoglobin prone to abnormal aggregation.

Contents

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]

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 insulin resistance: higher levels of valine are observed in the blood of diabetic mice, rats, and humans.[13] Mice fed a valine deprivation diet for one day have improved insulin sensitivity, and feeding of a valine deprivation 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 in reduced adiposity and improved insulin sensitivity.[15] The valine catabolite 3-hydroxyisobutyrate promotes skeletal muscle insulin resistance in mice by stimulating fatty acid uptake into muscle and lipid accumulation.[16] In humans, a protein restricted diet lowers blood levels of valine and 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

Source en.wikipedia.org