Commercial ergot supplements have been made from amino acids and their derivatives. They affect the release of anabolic hormones, the availability of fuel for activity, the ability to think clearly under pressure, and the prevention of muscular damage brought on by exertion. They are regarded as advantageous synergistic food ingredients [1].

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
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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

[1]. Effects of amino acid derivatives on physical, mental, and physiological activities. Crit Rev Food Sci Nutr. 2015;55(13):1793-1144.

L-Isoleucine is the L-enantiomer of isoleucine. It is found in Saccharomyces cerevisiae, Escherichia coli, plants, humans, algae, and mice, and is an important metabolite. Belonging to the aspartic acid family, it is a protein-synthesizing amino acid and also an isoleucine and L-α-amino acid. It is the conjugate base of L-isoleucine ononium, the conjugate acid of L-isoleucine acid, an enantiomer of D-isoleucine, and a zwitterion tautomer of L-isoleucine. It is an essential branched-chain aliphatic amino acid found in many proteins and is also an isomer of leucine. L-Isoleucine plays an important role in hemoglobin synthesis and the regulation of blood glucose and energy levels. L-Isoleucine is found in or produced by Escherichia coli (K12 strain, MG1655 strain). It has also been reported that L-isoleucine is present in Euphorbia plants (such as creeping euphorbia and hops) and other organisms with relevant data. Isoleucine is one of the nine essential amino acids for the human body (found in dietary proteins). Isoleucine has various physiological functions, such as promoting wound healing, detoxifying nitrogenous waste, stimulating immune function, and promoting the secretion of various hormones. Isoleucine is essential for hemoglobin formation and the regulation of blood sugar and energy levels, and is abundant in human muscle tissue. Isoleucine is particularly found in meat, fish, cheese, eggs, and most seeds and nuts. (NCI04) L-Isoleucine is one of the essential amino acids that the human body cannot synthesize on its own, and is known for its ability to enhance endurance and aid in muscle repair and rebuilding. This amino acid is particularly important for bodybuilders because it helps boost energy and aids in recovery from training. L-Isoleucine is also classified as a branched-chain amino acid (BCAA). It helps promote muscle recovery after exercise. Isoleucine is broken down for energy in muscle tissue. It plays an important role in hemoglobin synthesis and the regulation of blood sugar and energy levels. Leucine is an essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of leucine. It plays a crucial role in hemoglobin synthesis and the regulation of blood glucose and energy levels. Drug Indications Some branched-chain amino acids may possess anti-hepatic encephalopathy activity. They may also have anti-catabolism and anti-tardive dyskinesia activities. Mechanism of Action (Applicable to valine, leucine, and isoleucine) This group of essential amino acids is called branched-chain amino acids (BCAAs). Because the human body cannot synthesize this carbon atom arrangement, these amino acids are essential in the diet. The catabolism of these three compounds all begins in muscle, 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 transamination, using the same BCAA aminotransferase with α-ketoglutarate as the amine acceptor. This results in 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 various intermediates. The main product of valine is propionyl-CoA, a glucogenic precursor to 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 acetoacetyl-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 shorter lifespans and developmental abnormalities. The main neurological problems are due to poor myelination of the central nervous system. Amino acids are selectively used for protein synthesis by binding to transfer RNA (tRNA) in the cytoplasm. The amino acid sequence information of each protein is contained in the nucleotide sequence of messenger RNA (mRNA) molecules, which are synthesized from DNA fragments through transcription within the cell nucleus. The mRNA molecules then interact with various tRNA molecules in the cytoplasm, which are attached to specific amino acids, to synthesize the specific protein by linking individual amino acids together; this process is called translation, and it is regulated by amino acids (such as leucine) and hormones. Which specific proteins are expressed in a particular cell, and the relative rates of synthesis of different cellular proteins, depend on the relative abundance of different mRNAs and the availability of specific tRNA-amino acid combinations, and therefore also on the transcription rate and mRNA stability. From a nutritional and metabolic perspective, it is important to recognize that protein synthesis is a continuous process that occurs in most cells of the body. At homeostasis, protein synthesis is balanced with an equal amount of protein degradation when there is neither net growth nor net loss. Insufficient protein intake, or a low or absent level of certain essential amino acids (often called limiting amino acids) in the diet, primarily disrupts this balance, leading to a decrease in the rate of synthesis of certain proteins in the body, while protein degradation continues to provide an endogenous source for the most needed amino acids. /Protein Synthesis/
The mechanism of intracellular protein degradation, namely the hydrolysis of proteins into free amino acids, is more complex, and its mechanisms are not studied as thoroughly as those of protein synthesis. Cells contain various enzymes capable of hydrolyzing peptide bonds. However, most intracellular protein hydrolysis appears to be accomplished by two multi-enzyme systems: the lysosomal system and the proteasome system. Lysosomes are membrane-bound vesicles within the cell containing various proteolytic enzymes and primarily operate under acidic pH conditions. Large amounts of cytoplasm are phagocytosed by lysosomes (autophagy) and subsequently acted upon by proteases at high concentrations. This system is generally considered to have low selectivity, but it can still degrade specific intracellular proteins. This system is tightly regulated by hormones such as insulin and glucocorticoids, as well as by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, present in the cytoplasm. The first step involves linking ubiquitin molecules (basic peptides composed of 76 amino acids) to lysine residues of target proteins. Multiple enzymes participate in this process, selectively targeting proteins for degradation by the second component—the proteasome.

C6H13NO2

131.18

131.094

443-79-8

34464-35-2

6306

White to off-white solid powder

1.0±0.1 g/cm3

225.8±23.0 °C at 760 mmHg

210ºC

90.3±22.6 °C

0.0±0.9 mmHg at 25°C

1.463

0.73

2

3

3

9

103

2

CCC(C)C(C(=O)O)N

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: 50 mg/mL (381.16 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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