Absorption, Distribution and Excretion
Amino acids are absorbed from the small intestine via sodium-dependent active transport. Although free amino acids dissolved in body fluids constitute only a small fraction of the total amino acids in the body, they are essential for maintaining protein nutrition and metabolism. …While plasma is the easiest site for sampling, most amino acids are found in higher concentrations in intracellular pools. Typically, large neutral amino acids like leucine and phenylalanine are in near-equilibrium with their plasma concentrations. However, some other amino acids, particularly glutamine, glutamate, and glycine, are 10 to 50 times more concentrated in intracellular pools than in plasma. Dietary changes or pathological conditions can lead to significant variations in the concentrations of various free amino acids in plasma and tissue pools. /Amino Acids/ After ingestion, proteins are denatured by gastric acid and cleaved into smaller peptides by pepsin. Pepsin activity increases with the increase in gastric acid after eating. Proteins and peptides then enter the small intestine, where peptide bonds are hydrolyzed by various enzymes. These specific enzymes 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. These carrier systems target specific amino acids, dipeptides, and tripeptides, with each system targeting only a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are either secreted into the portal vein blood via other specific carrier systems within the mucosal cells or further metabolized intracellularly. The absorbed amino acids enter the liver, where some are absorbed and utilized; the remainder enters systemic circulation and is utilized by peripheral tissues. /Amino Acids/
The intracellular Plasmodium falciparum's amino acid requirement primarily derives from the digestion of host cell hemoglobin. However, adult hemoglobin lacks one amino acid—isoleucine—and therefore must obtain it from extracellular media. …The mechanism by which intracellular Plasmodium falciparum takes up isoleucine has been elucidated. Under physiological conditions, the isoleucine transport rate in human erythrocytes infected with mature trophozoite Plasmodium falciparum is approximately five times that of uninfected cells. This increased flux is achieved through novel permeability pathways (NPPs) induced by the parasite on the host cell membrane. Transport via nuclear transporters (NPPs) ensures that protein synthesis is not limited by the flux of isoleucine across the erythrocyte membrane. Once infecting erythrocytes, isoleucine is absorbed by the parasite through a saturable, ATP- and Na+-independent system that mediates the exchange inflow of isoleucine with leucine (released from hemoglobin). Accumulation of radiolabeled isoleucine within the parasite is mediated by a second (high-affinity, ATP-dependent) mechanism, potentially involving metabolism and/or isoleucine concentration within organelles.

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Metabolism/Metabolites
Liver
Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—unlike most other essential amino acids, the enzymes responsible for their catabolism are primarily located in extrahepatic tissues. Each amino acid undergoes a reversible amination 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 (BCKAD), 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) can produce both ketones and glucose. Once the amino acid deamination products enter the tricarboxylic acid cycle (TCA cycle, also known as the citric acid cycle or Krebs cycle) or glycolysis, their carbon skeletons can be used in biosynthetic pathways, particularly the synthesis of glucose and fats. Whether the amino acid's carbon skeleton ultimately produces glucose or fat depends on where it enters these pathways. If they enter as acetyl-CoA, they can only produce fat or ketone bodies. However, the carbon skeletons of other amino acids can somehow enter metabolic pathways, making their carbon atoms available for gluconeogenesis. This is the basis of the classical nutritional description of amino acids, which classifies them into ketogenic amino acids and glucogenic amino acids (i.e., those capable of producing ketone bodies [or fat] or glucose). Some amino acids produce both of these products upon degradation and are therefore considered ketogenic and glucogenic amino acids. /Amino Acids/
Mutations in the HSD17B10 gene were found in two previously reported cases of intellectual disability in men. A c.776G>C point mutation was found in one survivor (SV), while a potent c.419C>T mutation was found in another deceased case (SF), in which hydroxysteroid (17β) dehydrogenase 10 (HSD10) activity was undetectable. The protein levels of mutant HSD10 (R130C) in patient SF and mutant HSD10 (E249Q) in patient SV were approximately half those of the normal control group HSD10. The E249Q mutation appears to affect the interactions between HSD10 subunits, causing it to become an allosteric regulatory enzyme. This mutant enzyme catalyzes the NAD+ oxidation of allogeneinolone with a Hill coefficient of approximately 1.3. At low substrate concentrations, HSD10 (E249Q) fails to catalyze the dehydrogenation of 2-methyl-3-hydroxybutyryl-CoA and the oxidation of allogeneinolone (a positive regulator of the γ-aminobutyric acid type A receptor). Neurosteroid homeostasis is crucial for normal cognitive development, and mounting evidence suggests that blocking isoleucine catabolism alone typically does not lead to developmental disorders. These findings support the theory that neurosteroid metabolic imbalances may be a major cause of neurological dysfunction associated with hydroxysteroid (17β) dehydrogenase 10 deficiency. The HSD17B10 gene is located in the X chromosome Xp11.2 region, which is highly associated with X-linked intellectual disability. This gene encodes HSD10, a multifunctional mitochondrial enzyme that plays a vital role in the metabolism of neuroactive steroids and the degradation of isoleucine. The HSD17B10 gene consists of six exons and five introns. Its fifth exon is an alternative splicing exon, resulting in multiple HSD17B10 mRNA isoforms in the brain. One silent mutation (c.605C→A) and three missense mutations (c.395C→G; c.419C→T; c.771A→G) lead to X-linked intellectual disability, choreoathetosis and behavioral abnormalities (MRXS10), and hydroxyacyl-CoA dehydrogenase II deficiency, respectively…
Human type 10 17β-hydroxysteroid dehydrogenase (HSD) is a homotetrameric protein located in mitochondria. This enzyme was also formerly known as short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHSD). This NAD(H)-dependent dehydrogenase is crucial for the metabolism of branched-chain fatty acids and isoleucine…
Liver

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 condition 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 in the central nervous system. Interactions Branched-chain amino acids (BCAAs) have been shown to compete with other large and neutral amino acids (LNAAs, especially tryptophan and tyrosine) for membrane transport. Although BCAAs are not direct precursors to neurotransmitters, they can affect the transport of certain LNAAs across the blood-brain barrier, thereby affecting the concentration of certain neurotransmitters in the central nervous system.
...A high-leucine diet inhibits the growth of rats fed a low-protein diet, while supplementation with isoleucine and valine can prevent this growth inhibition.

[1]. l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats. Front Immunol. 2022 Jan 11;12:817583.

Therapeutic Uses
Proteins or mixtures of branched-chain amino acids (BCAAs), and in some cases, BCAAs alone, have been used to treat a variety of metabolic disorders. These amino acids have attracted considerable attention for reducing the uptake of aromatic amino acids by the brain and for increasing low circulating BCAA levels in patients with chronic liver disease and hepatic encephalopathy. They are also used in parenteral nutrition for patients with sepsis and other abnormalities.
/Experimental Treatment/ Upper gastrointestinal bleeding in patients with cirrhosis has a high mortality and morbidity rate. Post-bleeding catabolism is thought to be partly due to the low biological value of hemoglobin, which lacks the essential amino acid isoleucine. This study aimed to investigate the effects of simulated upper gastrointestinal bleeding on the metabolism of patients with cirrhosis and the efficacy of intravenous infusion of isoleucine. During routine portal venography, a multi-catheter technique was used to quantitatively analyze the protein kinetics of the viscera drained by the portal vein, including the liver, muscles, and kidneys. Sixteen metabolically stable patients who had fasted overnight received intragastric infusions of an amino acid solution simulating hemoglobin every 4 hours. They were then randomly assigned to either a saline group or an isoleucine group and received infusions of a stable isotope mixture (L-[cyclic-2H5]phenylalanine, L-[cyclic-2H4]tyrosine, and L-[cyclic-2H2]tyrosine) to measure organ protein kinetics. Simulated hemorrhage resulted in hypoisoleucinemia, which was alleviated by isoleucine infusion. Isoleucine infusion during hemorrhage resulted in a positive net phenylalanine balance in the liver and muscles, while protein kinetics in the kidneys and viscera drained by the portal vein were unaffected. No significant effect was observed in the control group…

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Pharmacodynamics
They provide the raw materials for the production of other essential biochemicals in the body, some of which are used to generate energy, stimulate the upper brain, and help you be more alert.

C6H13NO2

131.1729

131.094

73-32-5

34464-35-2

6306

Waxy, shiny, rhombic leaflets from alcohol
Crystals

1.0±0.1 g/cm3

225.8±23.0 °C at 760 mmHg

168-170ºC

90.3±22.6 °C

0.0±0.9 mmHg at 25°C

1.463

0.73

2

3

3

9

103

2

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

AGPKZVBTJJNPAG-WHFBIAKZSA-N

InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1

(2S,3S)-2-amino-3-methylpentanoic acid

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 : ~25 mg/mL (~190.59 mM)

Solubility in Formulation 1: 10 mg/mL (76.24 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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