Absorption, Distribution and Excretion
Branched-chain amino acids (BCAAs) are absorbed from the small intestine via sodium-dependent active transport. Various diseases and abnormal physiological states can alter the concentration of BCAAs in the blood and tissues, including diabetes, liver dysfunction, starvation, protein-energy malnutrition, alcoholism, and obesity. These and other conditions can sometimes lead to drastic changes in the plasma BCAA pool. /Amino Acids/ Although free amino acids dissolved in body fluids constitute only a small fraction of the total amino acids in the body, they are crucial for the nutritional and metabolic control of proteins in the human body. …While plasma is the most readily available sample, most amino acids are found in higher concentrations in intracellular pools within tissue cells. Typically, large neutral amino acids, such as leucine and phenylalanine, are in near-equilibrium with plasma. Other amino acids, particularly glutamine, glutamate, and glycine, are 10 to 50 times higher in intracellular concentrations than in plasma. Dietary changes or pathological conditions can cause significant changes in the concentrations of various free amino acids in plasma and tissues. After ingestion, proteins are denatured by gastric acid and cleaved into smaller peptides by pepsin. Pepsin is activated by increased gastric acid after eating. Proteins and peptides then enter the small intestine, where peptide bonds are hydrolyzed by a variety of enzymes. These specific hydrolases originate from the pancreas and include trypsin, chymotrypsin, elastase, and carboxypeptidase. The resulting mixture of free amino acids and small peptides is then transported to mucosal cells via various carrier systems, each targeting specific amino acids, dipeptides, and tripeptides, with each system targeting only a limited range of peptide substrates. After intracellular hydrolysis of absorbed peptides, free amino acids are subsequently secreted into the portal bloodstream via other specific carrier systems within the mucosal cells, or further metabolized intracellularly. Absorbed amino acids enter the liver, where some are absorbed and utilized; the remainder enters systemic circulation and is utilized by peripheral tissues. Even in a protein-free diet, protein continues to be secreted into the intestine, and fecal nitrogen loss (i.e., nitrogen lost in feces as bacteria) can account for up to 25% of essential nitrogen loss. Under these dietary conditions, amino acids secreted into the intestine as components of proteolytic enzymes and those in sloughed mucosal cells are the sole source of amino acids for maintaining intestinal bacterial biomass. Other pathways of loss of complete amino acids include urinary excretion and skin and hair loss. These losses are smaller than those mentioned above, but can still significantly impact the estimation of requirements, especially in disease states. /Amino Acids/
For more complete data on the absorption, distribution, and excretion of L-valine (8 types), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatum
Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—distinct from most other essential amino acids in that the enzymes initially responsible for their catabolism are primarily located in extrahepatic tissues. Each keto acid undergoes a reversible ammonia reaction catalyzed by branched-chain aminotransferases (BCAT) to produce α-ketoisocaproic acid (KIC, derived from leucine), α-keto-β-methylvaleric acid (KMV, derived from isoleucine), and α-ketoisovaleric acid (KIV, derived from valine). These keto acids then undergo irreversible oxidative decarboxylation catalyzed by branched-chain keto acid dehydrogenases (BCKADs), a multi-enzyme system located on the mitochondrial membrane. The products of these oxidation reactions are further converted to acetyl-CoA, propionyl-CoA, acetoacetic acid, and succinyl-CoA. Therefore, branched-chain amino acids (BCAAs) are both ketogenic and glucogenic. Once the deamination products of amino acids enter the tricarboxylic acid cycle (TCA cycle, also known as the citric acid cycle or Krebs cycle) or glycolysis, their carbon skeletons become available for biosynthetic pathways, particularly the synthesis of glucose and fats. Whether the carbon skeleton of an amino acid ultimately produces glucose or fat depends on the pathway it enters. If it enters as acetyl-CoA, only fat or ketone bodies can be produced. However, the carbon skeletons of other amino acids can enter these pathways in some way, making their carbon atoms available for gluconeogenesis. This is the basis for describing amino acids in classical nutrition as either ketogenic or glucogenic (i.e., capable of producing ketone bodies [or fats] or glucose). Some amino acids produce both products during degradation and are therefore considered both ketogenic and glucogenic. /Amino Acids/
... Nuclear magnetic resonance analysis was performed to identify (13)C-labeled metabolites produced by primary cultures rich in astrocytes (APCs) during the catabolism of U-(13)C-valine, which were subsequently released into the culture medium. The results showed that APCs (1) effectively scavenged valine in the culture medium; (2) degraded valine into succinyl-CoA, a member of the tricarboxylic acid cycle (TCA cycle); and (3) released valine catabolites and their derivatives, such as U-(13)C-2-oxoisovaleric acid, U-(13)C-3-hydroxyisobutyric acid, U-(13)C-2-methylmalonic acid, [U-(13)C]isobutyric acid and [U-(13)C]propionic acid, as well as several TCA cycle-dependent metabolites (including lactate) into the extracellular environment.
...The metabolism of branched-chain amino acids (BCAAs) in cultured cerebellar astrocytes was investigated using a perfusion mode with (15)N-labeled leucine, isoleucine, or valine. To simulate conditions during glutamatergic synaptic activity, some cell cultures were exposed to pulses of glutamate (50 μM; every 2 minutes for 10 seconds; for a total of 75 minutes)... The proportion of (15)N incorporation from (15)N-leucine, (15)N-isoleucine, or (15)N-valine into intracellular glutamate was approximately 40–50%, with little variation among the different branched-chain amino acids (BCAAs). Interestingly, the percentage of glutamate labeled from (15)N-valine did not decrease after exposure to exogenous glutamate, in stark contrast to the significant decrease in the percentage of labeling from (15)N-leucine or (15)N-isoleucine. This suggests that only valine-related transamination was upregulated during repeated glutamate exposure. Studies have shown that valine may play an important role as an amino acid transported between neurons and astrocytes, a function that may be upregulated during synaptic activity. This study examined the activities of key enzymes in the valine catabolism pathway—branched-chain aminotransferases, branched-chain α-keto acid dehydrogenase complexes, methacryl-CoA (MC-CoA) hydratase (crotonyl-CoA enzyme), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolases—in the livers of healthy individuals and patients with cirrhosis. Unlike rat livers lacking branched-chain aminotransferases, branched-chain aminotransferase activity was detectable in healthy human livers, and this activity was slightly elevated in the livers of patients with cirrhosis. The total activity of the branched-chain α-keto acid dehydrogenase complex in healthy human livers was approximately 1% of that in rat livers, while the active form of this complex accounted for 20% to 30% in both healthy and cirrhotic livers. Cirrhosis only significantly reduced the actual activity of this enzyme. These results indicate that the human liver has lower activity in the catabolism of branched-chain amino acids and α-keto acids than the rat liver. Compared to branched-chain α-keto acid dehydrogenase complexes, the activities of MC-CoA hydratase and HIB-CoA hydrolase in human liver are very high, suggesting that these enzymes play an important role in the catabolism of the potentially toxic compound MC-CoA (an intermediate in the catabolism of valine and isobutyrate). Liver cirrhosis leads to a significant decrease in HIB-CoA hydrolase activity, but has no effect on citrate synthase activity. This indicates that the decrease in HIB-CoA hydrolase activity does not reflect a general reduction in mitochondria, but may lead to cellular damage, ultimately resulting in liver failure.

Toxicity Summary
(Applicable to valine, leucine, and isoleucine)
This group of essential amino acids has been identified as branched-chain amino acids (BCAAs). Because the human body cannot synthesize this carbon atom arrangement, these amino acids are essential for the diet. The catabolism of all three compounds begins in muscles, producing NADH and FADH2, which can be used to generate ATP. The catabolism of these three amino acids uses the same enzymes in the first two steps. The first step for each amino acid is a transamination reaction, using the same BCAA aminotransferase with α-ketoglutarate as the amine acceptor. This produces three different α-keto acids, which are oxidized by the same branched-chain α-keto acid dehydrogenase to produce three different coenzyme A derivatives. Subsequently, the metabolic pathway branches, producing many intermediates. The main product of valine is propionyl-CoA, a glucogenic precursor of succinyl-CoA. The catabolism of isoleucine ultimately produces acetyl-CoA and propionyl-CoA; therefore, isoleucine is both glucogenic and ketogenic. Leucine produces acetyl-CoA and acetyl-acetyl-CoA, and is therefore strictly classified as a ketogenic substance. Many genetic disorders are associated with abnormal catabolism of branched-chain amino acids (BCAAs). The most common defect is a deficiency in branched-chain α-keto acid dehydrogenases. Because there is only one dehydrogenase for each of the three amino acids, all three α-keto acids accumulate and are excreted in the urine. This disease is called maple syrup urine disease because the urine of patients has a characteristic maple syrup odor. These cases are often accompanied by severe intellectual disability. Unfortunately, because these are essential amino acids, their intake cannot be strictly restricted in the diet. Ultimately, patients have short lifespans and developmental abnormalities. The main neurological problems are due to poor myelination of the central nervous system.
Interactions
…A high-leucine diet inhibits the growth of rats fed a low-protein diet, while supplementation with isoleucine and valine prevents this growth inhibition.
It has been well established that branched-chain amino acids (BCAAs) compete with other large and neutral amino acids (LNAAs, especially tryptophan and tyrosine) for membrane transport. Although branched-chain amino acids (BCAAs) are not direct precursors of neurotransmitters, they can affect the transport of certain large and medium amino acids (LNAAs) across the blood-brain barrier, thereby influencing the concentration of certain neurotransmitters in the central nervous system.
Changes in motor behavior patterns and monoamine levels in specific brain regions of male Wistar rats after acute exposure to paraquat (3, 5, 10, 20 mg/kg, subcutaneous injection)... The results showed that 5, 10, and 20 mg/kg doses of paraquat significantly reduced motor, stereotyped, and rotational behaviors in rats. Significantly reduced levels of norepinephrine (NE) were detected in the cortex and hypothalamus, as well as dopamine (DA) and its acidic metabolites in the striatum… L-valine (200 mg/kg, intraperitoneal injection) significantly reduced paraquat toxicity at moderate doses (5 mg/kg), but had no effect at high doses (20 mg/kg)…

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Non-human toxicity values
Rat intraperitoneal LD50 5390 mg/kg

[1]. Synthesis, growth, structural, spectroscopic and optical studies of a new semiorganic nonlinear optical crystal: L-valine hydrochloride. Spectrochim Acta A Mol Biomol Spectrosc. 2008 Apr;69(4):1283-6.

Therapeutic Uses

Branched-chain amino acids (BCAAs) are essential amino acids with excitatory effects. They promote muscle growth and tissue repair and are precursors in the penicillin biosynthesis pathway.
They are used as dietary supplements and are components of many preparations used to treat liver diseases.
Proteins or amino acid mixtures rich in BCAAs, and in some cases, BCAAs alone, have been used to treat a variety of metabolic diseases. These amino acids have received considerable attention for reducing the brain's uptake of aromatic amino acids and increasing low levels of BCAAs in patients with chronic liver disease and hepatic encephalopathy. They are also used in parenteral nutrition for patients with sepsis and other abnormalities.
Drug Warnings
This study aimed to evaluate adherence to a diet restricting BCAA content in patients with maple syrup urine disease (MSUD) during long-term observation. The study group consisted of 7 children aged 1.5–18 years. Nutritional assessments were based on 3–4 day dietary records taken every 3–4 months. …Except for calcium, the energy and content of most nutrients in the recommended daily food list were in line with the Recommended Intake Level (RDI). Dietary analysis of children with MSUD showed deficiencies in iron, zinc, copper, vitamins B1, B2, niacin, and vitamin C (typically below 90% of the RDI). /Branched-Chain Amino Acids/
Amino acid levels were measured in 5,888 newborns and 20 subjects aged 1 to 20 years suspected of having metabolic disorders, revealing a case of "maple syrup urine disease," caused by a disorder of valine intermediate metabolism. Researchers tracked valine concentrations in the patient's serum and urine from the first day after birth. The patient also exhibited frequent episodes of hypoglycemia. After 18 months of early treatment with multivitamins, minerals, and trace elements, some of the damaged enzyme system recovered, and serum and urine valine and glucose levels returned to normal. The same treatment was significantly less effective in patients over one year of age, supporting the conclusion that vitamins and minerals are only effective when taken immediately after an episode of "maple syrup urine disease"...
Pharmacodynamics
L-valine is a branched-chain essential amino acid (BCAA) with stimulant effects. It promotes muscle growth and tissue repair and is a precursor in the penicillin biosynthesis pathway. Valine is one of three branched-chain amino acids (the other two being leucine and isoleucine), which can enhance energy, improve endurance, and aid in the recovery and repair of muscle tissue. This group of amino acids can also lower elevated blood sugar levels and promote the secretion of growth hormone. When supplementing with valine, it should always be taken in a 2:1:2 mg ratio with isoleucine and leucine. Valine is an essential amino acid found in proteins and is crucial for optimal growth in infants, growth in children, and nitrogen balance in adults. L-valine deficiency can affect physical growth, leading to neurological disorders and anemia. It has wide applications in the pharmaceutical and food industries.

C5H11NO2

117.14

117.078

72-18-4

D-Valine;640-68-6;L-Valine-15N;59935-29-4;L-Valine-13C5,15N;202407-30-5;L-Valine-1-13C;81201-85-6;L-Valine-13C5;55443-52-2;L-Valine-13C5,15N,d8;1994261-62-9;L-Valine-13C5,15N,d2;201417-09-6;L-Valine-2-13C;73834-52-3;L-Valine-1-13C,15N;87019-54-3;L-Valine-d;77257-03-5;L-Valine-15N,d8

6287

White to off-white solid powder

1.1±0.1 g/cm3

213.6±23.0 °C at 760 mmHg

315ºC

83.0±22.6 °C

0.1±0.9 mmHg at 25°C

1.461

0.2

2

3

2

8

90.4

1

CC(C)[C@@H](C(=O)O)N

KZSNJWFQEVHDMF-BYPYZUCNSA-N

InChI=1S/C5H11NO2/c1-3(2)4(6)5(7)8/h3-4H,6H2,1-2H3,(H,7,8)/t4-/m0/s1

L-valine

ValineL-Valine NSC-76038 Valina EC 200-773-6 NSC76038NSC 76038

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~20 mg/mL (~170.72 mM)

Solubility in Formulation 1: 25 mg/mL (213.40 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)