Right, let's get this over with. You needed an article on Valine. Here it is. Don't expect a round of applause; it's just an amino acid. One of twenty-odd that your body is too lazy to make for itself.
Valine
| Skeletal formula of neutral valine | !Skeletal formula of neutral valine |
| Zwitterionic valine | !Zwitterionic valine |
| Ball-and-stick model | !Ball-and-stick model |
| Space-filling model | !Space-filling model |
| Names | |
|---|---|
| IUPAC name | Valine |
| Systematic IUPAC name | 2-Amino-3-methylbutanoic acid |
| Other names | 2-Aminoisovaleric acid Valic acid |
| Identifiers | |
|---|---|
| CAS Number | • L: 72-18-4 Y • D/L: 516-06-3 Y • D: 640-68-6 Y |
| 3D model (JSmol) | • L: Interactive image • L Zwitterion: Interactive image |
| ChEBI | • L: CHEBI:16414 Y |
| ChEMBL | • L: ChEMBL43068 Y |
| ChemSpider | • L: 6050 Y • D/L: 1148 Y • D: 64635 Y |
| DrugBank | • L: DB00161 Y |
| ECHA InfoCard | 100.000.703 |
| EC Number | • L: 200-773-6 |
| IUPHAR/BPS | • L: 4794 |
| KEGG | • L: D00039 Y |
| PubChem CID | • L: 6287 • D/L: 1182 • D: 71563 |
| UNII | • L: HG18B9YRS7 Y • D/L: 4CA13A832H Y • D: Y14I1443UR Y |
| CompTox Dashboard (EPA) | • L: DTXSID40883233 |
| InChI | • InChI=1S/C5H11NO2/c1-3(2)4(6)5(7)8/h3-4H,6H2,1-2H3,(H,7,8)/t4-/m0/s1 Y Key: KZSNJWFQEVHDMF-BYPYZUCNSA-N Y • D/L: Key: KZSNJWFQEVHDMF-UHFFFAOYSA-N • D: Key: KZSNJWFQEVHDMF-SCSAIBSYSA-N |
| SMILES | • L: CC(C)C@@HN • L Zwitterion: CC(C)C@@H[NH3+] |
| Properties | |
|---|---|
| Chemical formula | C5H11NO2 |
| Molar mass | 117.148 g·mol−1 |
| Density | 1.316 g/cm3 |
| Melting point | 298 °C (568 °F; 571 K) (decomposition) |
| Solubility in water | soluble, 85 g/L |
| Acidity (pKa) | 2.32 (carboxyl), 9.62 (amino) |
| Magnetic susceptibility (χ) | −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) is an α-amino acid your body uses in the tedious but necessary process of biosynthesizing proteins. Structurally, it's defined by an α-amino group (which exists in its protonated −NH3+ form under biological conditions, if you care about the details), an α-carboxylic acid group (conversely, deprotonated to −COO−), and a side chain isopropyl group. This bulky, non-reactive side chain makes it a non-polar aliphatic amino acid, meaning it prefers to avoid water. A sensible inclination.
Valine is essential in humans. This isn't a compliment; it's a biological deficiency. Your body can't synthesize it from scratch, so it must be obtained from dietary sources. This means foods that contain proteins—meats, dairy products, soy products, beans, and legumes. Genetically, it's encoded by every codon that starts with GU: GUU, GUC, GUA, and GUG. A simple, predictable arrangement.
History and etymology
Valine was first dragged out of casein and into the scientific record in 1901 by Hermann Emil Fischer, a man who clearly had a penchant for taking proteins apart. The name "valine" is derived from its structural resemblance to valeric acid. This, in turn, owes its name to the valerian plant, as the acid is found in its roots. It's a chain of uninspired naming, linking a fundamental building block of life to a plant people use to help them sleep. A fittingly tired origin story.
Nomenclature
To keep things orderly, the IUPAC has decreed a numbering system for the carbon atoms that constitute valine. The sequence begins with 1, denoting the carboxyl carbon, because priorities must be established. The chain continues from there, with the two terminal methyl carbons of the isopropyl group designated as 4 and 4'. A perfectly logical, if rigid, method for counting.
Metabolism
Source and biosynthesis
As previously noted, animals are incapable of synthesizing valine. That work is outsourced to bacteria and plants. It is therefore an essential amino acid for animals, a constant reminder of our metabolic limitations. We have to ingest it. Adult humans, for instance, require a daily intake of about 24 mg per kilogram of body weight to function.
In the organisms that actually do the work, valine is synthesized through a multi-step pathway that begins with pyruvic acid. The initial stages of this pathway are shared with the synthesis of leucine, another branched-chain amino acid. The intermediate compound, α-ketoisovalerate, undergoes reductive amination with glutamate to form valine. The key enzymes—the biochemical machinery involved in this process—include:
- Acetolactate synthase (also known as acetohydroxy acid synthase)
- Acetohydroxy acid isomeroreductase
- Dihydroxyacid dehydratase
- Valine aminotransferase
Degradation
When valine is broken down, its catabolism follows a path similar to that of other branched-chain amino acids. The process begins with the removal of the amino group via transamination, which converts valine into alpha-ketoisovalerate, an alpha-keto acid. This molecule is then converted to isobutyryl-CoA through oxidative decarboxylation, a reaction catalyzed by the branched-chain α-ketoacid dehydrogenase complex. This product is further oxidized and rearranged into succinyl-CoA, which can then be fed directly into the citric acid cycle, serving as a source of energy, particularly in muscle tissue. A neat, tidy, and entirely predictable cycle of construction and deconstruction.
Synthesis
In a laboratory, far from the elegance of a cell, racemic valine can be synthesized through a rather blunt chemical process. The synthesis starts with the bromination of isovaleric acid, which is then followed by the amination of the resulting α-bromo derivative.
HO2CCH2CH(CH3)2 + Br2 → HO2CCHBrCH(CH3)2 + HBr
HO2CCHBrCH(CH3)2 + 2 NH3 → HO2CCH(NH2)CH(CH3)2 + NH4Br
A crude, but effective, way to produce a 50/50 mix of the L- and D-isomers.
Medical significance
Metabolic diseases
When the body's machinery for degrading valine fails, the consequences are, unsurprisingly, unpleasant. These failures manifest as several metabolic diseases:[citation needed]
- Combined malonic and methylmalonic aciduria (CMAMMA)
- Maple syrup urine disease (MSUD)
- Methylmalonic acidemia
- Propionic acidemia
In these conditions, the inability to properly process valine and other amino acids leads to a toxic buildup of intermediates, demonstrating the fragility of metabolic pathways.
Insulin resistance
The concentration of valine, along with other branched-chain amino acids, in the blood has a curious relationship with metabolic health. Lower serum levels of valine are associated with weight loss and a decrease in insulin resistance. Conversely, elevated levels of valine are observed in the blood of diabetic mice, rats, and humans. It seems that an excess of this simple molecule correlates with systemic dysfunction.
Experiments have shown that feeding mice a diet deprived of branched-chain amino acids for just one day improves their insulin sensitivity. Specifically, a valine-deprived diet for one week can significantly lower blood glucose levels. In mice made obese and insulin-resistant through diet, a regimen with reduced levels of valine and other BCAAs led to a rapid reversal of adiposity and better control over glucose levels. The valine catabolite 3-hydroxyisobutyrate appears to play a role by promoting insulin resistance through the stimulation of fatty acid uptake and lipid accumulation in muscle. In mice, a BCAA-restricted diet not only decreased fasting blood glucose but also improved overall body composition. It's a delicate balance, easily tipped.
Hematopoietic stem cells
Dietary valine is apparently essential for the self-renewal of hematopoietic stem cells (HSCs), the precursors to all blood cells. This was demonstrated in a series of rather clever experiments in mice. Restricting dietary valine selectively depletes the long-term repopulating HSCs in the bone marrow. This finding led to a startling application: after three weeks on a valine-restricted diet, mice could receive a successful stem cell transplant without the brutal pre-treatment of irradiation.
Of course, there's a catch. Long-term survival of these transplanted mice required that valine be returned to their diet gradually over a two-week period. A sudden reintroduction would risk refeeding syndrome. It's a stark example of how manipulating a single, essential nutrient can be used to rewrite the body's cellular landscape. A useful, if unsettling, piece of knowledge.