Polar vs Nonpolar Amino Acids (2025)

What are polar and nonpolar amino acids?

The characteristics of the side chains of amino acids are used to categorize them. These side chains are responsible for determining the amino acids' solubility, interactions, and positions within protein structures. These are polar amino acids that have side chains that are capable of forming hydrogen bonds with water, which makes them hydrophilic (attractive to water). The hydroxyl (-OH), amine (-NH₂), thiol (-SH), or carboxamide (-CONH₂) groups that are present in their side chains are potentially present. Those amino acids that are nonpolar and have side chains that are devoid of hydrophilic groups and are unable to establish hydrogen bonds with water. These substances are hydrophobic, which means they resist water, and they often include aromatic groups or hydrocarbons.

The 20 common amino acids. (S Maloy., 2013)

Difference between polar and nonpolar amino acids

(1) Hydrophobicity

Because of the presence of polar side chains, polar amino acids are hydrophilic, which means that they attract water. This property makes them soluble in water. The majority of the time, they are found on the surface of proteins and interact with surroundings that include water sources. They are insoluble in water because they are hydrophobic, which means they reject water. Nonpolar amino acids are water-repelling. In order to avoid being exposed to water, they are often buried inside proteins that have a hydrophobic core.

(2) Solubility

Amino acids that are polar have side chains that are capable of forming hydrogen bonds or ionic bonds with water and other molecules that are also polar. Examples of the types of groups that are frequently found on their side chains include hydroxyl (-OH), amide (-CONH₂), thiol (-SH), carboxyl (-COOH), and amine (-NH₂). Because of this, they are soluble in water because of the polar or charged character that they possess. Nonpolar amino acids have side chains that are hydrophobic, which means they reject water, and they do not form hydrogen bonds with water. The majority of their side chains are made up of sulfur-containing groups, aromatic rings, or hydrocarbon chains. Therefore, despite the fact that they are soluble in water in their whole, it is possible that they are not as soluble in water as polar amino acids.

(3) Protein location

Amino acids with polar groups are located on the surface of proteins and interact with water and other polar substances. Potentially, they contribute to the structure of proteins via ionic interactions and hydrogen bonding. Proteins are structurally stable because of the hydrophobic core, which is composed of nonpolar amino acids. Because of the hydrophobic impact, they are essential for proper protein folding and stability.

(4) Charge

Nonpolar amino acids are neutral and uncharged at normal pH. Some polar amino acids are charged at physiological pH, such as aspartic acid, glutamic acid, lysine, and arginine. Certain polar amino acids are neutral but exhibit polarity owing to their capacity to form hydrogen bonds (e.g., Serine, Threonine, Asparagine, Glutamine).

List of amino acids and their occurrence frequency. (Kaur R., et al., 2015)

The 20 amino acids found in proteins (list 1). (Amaya-Farfan J., et al., 2003)

The 20 amino acids found in proteins (list 2). (Amaya-Farfan J., et al., 2003)

Polar amino acids: characteristics and examples

(1) Arginine Amino Acids

With the formula HOOCCH(NH₂)(CH₂)₃NH(C=N⁺H₂)NH₂, arginine (Arg or R) (2-amino-5-(diaminomethylidene amino)-pentanoic acid) is a polar, basic, positively charged amino acid made up of a four-carbon aliphatic straight chain. A guanidinium group is the outside portion of the side chain that is made up of three nitrogens bound to a carbon atom. The side chain of Arg can only act as a donor of hydrogen bonds because of the conjugation between the double bond and the nitrogen lone pairs. Nitric oxide (NO), a crucial biological messenger, is made from arg. Peptides that include arg have the potential to generate piperidones. While the side chains of Ser, Thr, Asn, and Gln may act as both donors and acceptors of hydrogen bonds, the side chains of Arg and Trp can only act as hydrogen donors.

(2) Asparagine Amino Acids

With the formula HOOCCH(NH₂)CH₂CONH₂, asparagine (Asn or N) ((2S)-2-amino-3-carbamoyl-propanoic acid) is a polar, uncharged amino acid. Its side chain's functional group is a carboxyamide. Either Asn or Asp are represented by Asx or B. Asn are often located close to the start and finish of alpha helices, which are then motifs in beta sheets.

(3) Aspartic acid Amino Acids

The formula of aspartic acid, often known as D or Asp, is HOOCCH(NH₂)CH₂COO⁻. It is a negatively charged, polar, acidic amino acid. Because their side chains are normally negatively charged at physiological pH, these amino acids are often referred to as aspartate (Asp) and glutamate (Glu), respectively. General acids Asp and Glu are essential for enzyme active sites, protein solubility, and ionic character maintenance.

(4) Cysteine Amino Acids

Cysteine, abbreviated as Cys or C, is an uncharged polar amino acid having the molecular formula HOOCCH(NH₂)CH₂SH. It is a hydrophilic amino acid that contains sulfur and is an essential thiol-containing amino acid. A key component in protein structure, Cys's sulfhydryl is very reactive and forms disulfide bonds.Because of its nucleophilicity, the Cys thiol group may be readily oxidized to cystine disulfide. Because thiols may participate in redox processes, Cys is an antioxidant. Protein crosslinking is an important function of cysteine residues. One protein that exhibits cystine crosslinking is insulin. In order to rid the body of dangerous pollutants, Cys is helpful.

(5) Glutamic acid Amino Acids

The polar amino acid glutamic acid, abbreviated as Glu or E, has the molecular formula HOOCCH(NH₂)CH₂CH₂COOH. An acidic side chain is included in it. As for glutamate, it's the building block for glutamine, proline, and arginine, and serine for glutamine and cysteine.

(6) Glutamine Amino Acids

Glutamine, often known as Q or Gln, is an uncharged polar amino acid having the molecular formula HOOCCH(NH₂)(CH₂)2CONH₂. Gln or Glu may be represented by the acronyms Glx or Z, respectively. In lieu of the carboxylate, the side chain has an amide group, making it similar to the acidic amino acid Glu's amide. When it comes to non-essential amino acids found in nature, Gln is by far the most prevalent. When you're sick or hurt, it becomes conditionally necessary. In nitrogen metabolism, glutamate and Gln both have important functions.

(7) Histidine Amino Acids

Histidine (His or H) (2-amino-3-(3H-imidazol-4-yl) propanoic acid) is a polar, basic amino acid having the molecular formula HOOCCH(NH₂)CH₂ (C=CHNHCH=N⁺H). Histidine can exist in either an uncharged or positively charged state and is often located at enzyme active sites, where its imidazole ring can easily transition between both states, facilitating bond formation and cleavage. The unprotonated imidazole acts as a nucleophile and functions as a general base, while the protonated version operates as a general acid. The imidazole moiety contributes to the stabilization of protein-folded structures and serves as a coordinating ligand in metalloproteins. The intramolecular nucleophilic assault by the imidazole nitrogen may lead to lactam production and the cleavage of peptide bonds.

(8) Serine Amino Acids

The formula for the polar, neutral, uncharged amino acid serine (Ser or S) ((S)-2-amino-3-hydroxypropanoic acid) is HOOCCH(NH₂)CH₂OH. It may be thought of as a hydroxylated form of Ala and possesses an aliphatic hydroxyl side chain. Ser is a precursor of various amino acids, such as Gly, Cys, and Trp (in bacteria), and it plays a role in the biosynthesis of purines and pyrimidines. It is also found in enzymes like α-chymotrypsin and is the precursor to many other metabolites, including sphingolipids. Aspartate, Asn, and Ser break apart α helices.

(9) Threonine Amino Acids

With the formula HOOCCH(NH₂)CHOHCH₃, threonine (Thr or T) ((2S,3R)-2-amino-3-hydroxybutanoic acid) is a polar, uncharged amino acid with an aliphatic hydroxyl side chain. Thr is one of the three proteinogenic amino acids having an alcohol group, along with Ser and Tyr. One may think of Thr as a hydroxylated form of Val. There are two potential diastereomers of l-Thr or four possible stereoisomers of Thr with two chiral centers. Nevertheless, only one enantiomer, (2S,3R)-2-amino-3-hydroxybutanoic acid, is referred to by the term l-Thr. L-allo-Thr is the name of the second diastereomer (2S,3S), which is almost ever seen in nature. Because of the hydroxyl group's ability to form hydrogen bonds, both Ser and Thr are often regarded as hydrophilic and are essential to the operation of biological processes. The dietary habits of animals have been shown to be impacted by Thr.

(10) Tyrosine Amino Acids

(4-hydroxyphenylalanine ((S)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) Tyrosine (Tyr or Y) has the formula HOOCCH(NH₂)CH₂C₆H₅OH and is a polar, neutral, aromatic amino acid. It is the precursor to dopamine, thyroxin, norepinephrine (noradrenaline), epinephrine (adrenaline), and the color melanin. Hypothyroidism may arise from a deficiency in this amino acid, which is the precursor for the thyroid gland hormone thyroxin. Tyr's high water solubility has been a helpful characteristic in separating this amino acid from protein hydrolysates. Tyrosine O-sulfate has been shown to be present in human urine and fibrinogen.

Nonpolar amino acids: characteristics and examples

(1) Alanine Amino Acids

The formula for aliphatic amino acid alanine, which is written as Ala or A, is HOOCCH(NH₂)CH₃. It is nonpolar, neutral, and aliphatic. The movement of nitrogen from the skeletal muscles to the liver is facilitated by Ala.

(2) Glycine Amino Acids

Glycine (Gly or G), also known as aminoacetic acid or aminoethanoic acid, is a nonpolar, neutral, aliphatic amino acid having the chemical formula HOOCCH(NH₂)H. Glycine is the most basic amino acid and has crucial functions in peptide and protein structures. It lacks a side chain, enabling it to accommodate secondary structures inaccessible to bigger amino acids. Glycine operates as a neurotransmitter in the central nervous system, performing several roles. Glycine is a precursor of porphyrins. Glycine, Proline, Aspartate, Serine, and Asparagine facilitate reverse turns. The acylated amino group of Gly may take an additional acyl group, resulting in the formation of a diacylamide.

Role of Polar and Nonpolar Amino Acids

(3) Isoleucine Amino Acids

Isoleucine (Ile or I), chemically known as (2S,3S)-2-amino-3-methylpentanoic acid, is a nonpolar, neutral, aliphatic amino acid having the molecular formula HOOCCH(NH₂)CH(CH₃)CH₂CH₃. Isoleucine, with a hydrocarbon side chain, is categorized as a hydrophobic amino acid. Alongside Thr, Ile is one of the two prevalent amino acids possessing a chiral center. Despite the possibility of four stereoisomers of Ile, the naturally occurring form is only (2S,3S)-2-amino-3-methylpentanoic acid.

(4) Lysine Amino Acids

Lysine (Lys or K), also known as 2,6-diaminohexanoic acid, is a positively charged amino acid with the chemical formula HOOCCH(NH₂)(CH₂)₄N⁺H3. Lysine, arginine, and histidine possess fundamental side chains. The ε-amino group often engages in hydrogen bonding and acts as a general base in catalysis. Lysine contributes to collagen synthesis and is essential for optimal growth and bone development.

(5) Methionine Amino Acids

The neutral amino acid methionine, abbreviated as Met or M, has the molecular formula HOOCCH(NH₂)CH₂CH₂SCH₃. One of the two proteinogenic amino acids that include sulfur, Met is also an excellent antioxidant, along with Cys. Adenosyl methionine, a byproduct of it, is a methyl donor.

(6) Phenylalanine Amino Acids

With a formula HOOCCH(NH₂)CH₂C₆H₅. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and, phenylalanine (Phe or F) is a neutral, aromatic amino acid. The hydrophobic character of the benzyl side chain defines it as nonpolar. Not just in protein structure but also as crucial precursors for thyroid and adrenocortical hormones as well as in the production of neurotransmitters like dopamine and noradrenaline, Tyr and Phe are vital components. The inability to breakdown Phe is the hereditary condition known as phenylketonuria (PKU). This is brought on by a phenylalanine hydroxylase deficit, which causes Phe to build up in bodily fluids. Those with this condition, known as "phenylketonurics," have to refrain from Phe intake. Artificial sweetener aspartame (l-aspartyl-l-phenylalanine methyl ester) is a nonfood source of Phe; the body breaks it down into numerous byproducts including Phe. Phe's side chain is immune from side reactions; nonetheless, during catalytic hydrogenation the aromatic ring may be saturated and transformed into a hexahydrophenylalanine residue.

(7) Proline Amino Acids

Proline (Pro or P) ((S)-pyrrolidine-2-carboxylic acid) is a nonpolar, neutral amino acid recognized as a helix disruptor. It has an aliphatic side chain; nonetheless, it distinguishes itself from other amino acids by having its side chain connected to both the α-carbon and nitrogen. Pro has a secondary amino group instead of a primary one, categorizing it as an imino acid. Due to the absence of a hydrogen atom on the amide group, Pro cannot function as a hydrogen bond donor, but can only serve as a hydrogen bond acceptor. Pro is the only residue that results in a N-alkyl amide bond when integrated into a peptide. Pro is distinctive due to the absence of an amide proton for hydrogen bonding and the presence of a cyclic side chain, which imposes conformational constraints; the pyrrolidine ring reduces the conformational flexibility of the DKP moiety, resulting in well-defined side-chain rotamers for the nonprolyl residue. Proline may induce a reversal in the orientation of peptide chains inside globular proteins and serves as a conformational factor in structural proteins, such as collagen. Brandl and Deber proposed that the cis–trans isomerism of Pro residues may influence the transduction of transmembrane proteins. The incorporation of Pro in DKPs enhances the solubility of the compounds in chloroform (CHCl₃). Moreover, investigations have shown that Pro has the capacity to isomerize, transitioning from the all-cis form (polyproline 1) to the all-trans form (polyproline 11). Pro is present in naturally occurring physiologically active peptides, such as peptide hormones including angiotensin, bradykinin, oxytocin, vasopressin, melanocyte-stimulating hormone (MSH), thyroid-releasing factor (TRF), as well as gramicidin S, actinomycin, and antamanide. Dipeptides with a proline or hydroxyproline residue have a significant inclination for intramolecular cyclization, and it is unsurprising that several proline-based diketopiperazines are found in fermented and thermally processed foods. Moreover, the heat processing of food seems to enhance the preservation of some amino acids over others. During the roasting of coffee beans, there is a decrease in the quantity of amino acids by 20–40%. The levels of reactive amino acids, such as lysine, are significantly reduced, while others, such as proline or phenylalanine, remain relatively stable. Peptides containing Proline and Glycine have a greater likelihood of cyclization compared to those containing other amino acids.

(8) Tryptophan Amino Acids

α-amino-β-[3-indolyl]propionic acid, 1-β-indolylalanine, 2-amino-3-indolylpropionic acid, and (S)-2-amino-3-(1H-indol-3-yl)-propionic acid are all forms of tryptophan (Trp or W), a nonpolar, neutral, aromatic amino acid with an indole ring bonded to the methylene group. An indole ring is present in a large number of pharmacologically active substances that are being sold today. They are used therapeutically to treat Parkinson's disease, migraines, hypertension, and antiemetics and anti-inflammatories. A key neurotransmitter in the brain, 5-hydroxytryptamine (5-HT), often referred to as serotonin, is also derived from Trp. Trp is very sensitive to acidic environments, and its side chain is vulnerable to sulfenyl chloride replacement, dimerization, oxidative degradation, and alkylation.

(9) Valine Amino Acids

With the formula HOOCCH(NH₂)CH(CH₃)2, valine (Val or V) ((S)-2-amino-3-methyl-butanoic acid) is a neutral, nonpolar, aliphatic amino acid. High amounts of Val, a branched-chain amino acid, are present in muscles together with Leu and Ile. Val is required for tissue regeneration, muscle metabolism and coordination, and the preservation of the body's ideal nitrogen equilibrium. Side reactions rise as a consequence of the steric barrier in Val and Ile, which is brought on by branching and reduces the rate of coupling reactions.

Role of polar and nonpolar amino acids

(1) Regulate immune functions

Alanine serves as a primary substrate for hepatic glucose production, a crucial energy source for leucocytes, hence impacting immunological function. Supplementation with 2 mm-alanine in the culture media has been shown to inhibit apoptosis, promote cell proliferation, and increase antibody production in B-lymphocyte hybridoma. The supplementary concentration of alanine is around 2–4 times higher than that in the plasma of animals and constitutes 8% of the concentration seen in ovine allantoic fluid on day 60 of gestation. The precise mechanism remains unidentified, however it may include alanine-mediated regulation of protein breakdown in immunocytes, similar to findings in hepatocytes via cellular signaling pathways. Currently, there is less evidence about the impact of dietary alanine supplementation on the immunological response across any animal species. In patients receiving total parenteral nutrition (TPN), the incorporation of alanine may significantly enhance gluconeogenesis and leukocyte metabolism.

The maximum proliferation of human and rodent T lymphocytes in response to mitogens and the killing of tumor cells by activated macrophages are both facilitated by 0.2 mm-arginine, which is near to its post-absorptive level in plasma, according to early in vitro investigations. Additional data suggests that monocyte and NK cell cytotoxicity is enhanced in vitro by high arginine concentrations (e.g., 2 mm). Keep in mind that certain bodily fluids have an extracellular arginine content greater than 2 mm. In early pregnancy, for instance, the content of arginine in swine allantoic fluid might reach 4-6 mm. An important defense mechanism against viruses, bacteria, fungi, malignant cells, intracellular protozoa, and parasites in birds, mammals, terrestrial animals, low vertebrates (such as freshwater and marine fish), and invertebrates (like shrimp) has been determined by extensive research conducted over the last ten years: NO synthesis in macrophages and neutrophils by inducible NO synthase (iNOS). In response to IFNγ and lipopolysaccharide (LPS), leucocytes promote iNOS expression, and NO is now acknowledged to have a significant function in both innate and acquired immunity. Consequently, the immune response is mainly affected by NO generation by iNOS. Leucocyte NO production is heavily dependent on arginase expression and activity regulation due to the fact that arginase and iNOS share the substrate arginine. Helicobacter pylori is one example of a bacterium that has evolved a technique to evade NO death by constitutively expressing arginase, an enzyme that depletes arginine and makes it less available for NO generation by iNOS. An intriguing new discovery is that the expression of the T-cell receptor ξ chain (CD3Ύ), which is necessary for the integrity of the T-cell receptor, is modulated by normal levels of arginine, for example, 150 μm. In early pregnancy, the synthesis of CD3ξ was enhanced by lengthening the half-life of its mRNA when citrulline was added to the culture medium at concentrations of 0.1 mm (around its plasma level) or 1 mm (10% of its concentration in ovine allantoic fluid). This finding lends credence to the idea that citrulline may be used to raise blood arginase activity and, therefore, arginine availability in immunodeficient patients.

Roles of amino acids in immune responses. (Li P., et al., 2007)

(2) Regulation of the nervous system

Similar in structure to glutamate, but having one less methylene (-CH₂) group on the sidechain, is aspartate. Although aspartate and glutamate may be co-released, l-aspartate is more often thought of as the secondary excitatory neurotransmitter in the central nervous system, and it was first shown to stimulate neurons in conjunction with l-glutamate. While l-glutamate's function as the brain's primary excitatory neurotransmitter is well-established and accepted, l-aspartate's neurotransmitter status is still up for debate.

Visual cortex, hippocampus, and cerebellum are just a few of the brain areas that have been shown to emit l-aspartate in response to certain stimuli. Concentrations in different parts of the brain might vary (e.g., the hippocampus contains 0.6 nmol/mg tissue), but it was found in the rat brain at about 2.7 µmol/g wet weight. Oxaloacetate and glutamate undergo a process mediated by l-aspartate transaminase to produce the majority of it. A method for the elimination of l-aspartate was shown by Storck's team to be excitatory amino acid transporter 1 (EAAT1), also known as the glutamate aspartate transporter 1 (GLAST-1). Since l-aspartate is not transported by the same transporters as l-glutamate and there have been conflicting reports of potential transporters such sialin, the exact mechanism of vesicular transport is still unknown. Although l-aspartate is a well-documented NMDA receptor selective agonist, research conducted by Herring's group shown that the release of only l-aspartate is not enough to activate NMDA receptors in the hippocampus. In addition, aspartate was not shown to be more abundant in a recent profile of synaptic vesicles derived from neurons in the cortex. On the other hand, Richards's group discovered that motoneuron synapses contained more aspartate than glutamate, which raises the prospect of aspartate-evoked activation of spinal cord NMDA receptors being physiologically relevant. There are currently no known receptors for l-aspartate. Therefore, l-aspartate signaling's relevance is still up for debate.

The neurological effects of serine are similar for its two enantiomers. As a precursor for neuroactive chemicals, l-Serine also functions as an essential component in development and signaling. Numerous neuropathies and developmental problems have been associated to insufficiencies of l-Serine, which is produced in the brain by astrocytes via four distinct mechanisms. A female patient with a case study of developmental delays had ichthyosis, delayed puberty, polyneuropathy, and stunted growth, among other symptoms. According to research by Buratta and others, l-serine may have a role in the ethanolamine-mediated extracellular release of glutamate and aspartate. Additional in vitro research has shown that l-serine treatment promotes dendritic formation in hippocampus slices and an increase in the number of Purkinje fibers in the cerebellum. Along with its role in development and the release of other neurotransmitters made of amino acids, l-serine is an important building block for glycine and d-serine, the latter of which is produced by serine racemase.

(3) Nutrient metabolism and oxidative defense

There is evidence that amino acids (AAs) are involved in cellular signaling, nutrition metabolism unique to cells, oxidative stress, and protein consumption efficiency. One example is the mitochondrial enzyme N-acetylglutamate synthase, which arginine activates allosterically. This enzyme takes glutamate and acetyl-CoA and turns them into N-acetylglutamate, which is an allosteric activator of carbamoylphosphate synthase I. Arginine and glutamate keep the urea cycle in the liver active, which helps detoxify ammonia. Secondly, alanine controls gluconeogenesis and glycolysis to make sure that hepatocytes produce net glucose when food is scarce. This regulation is accomplished by inhibiting pyruvate kinase. Thirdly, glutamate and aspartate control cellular redox status and glycolysis by mediating the transport of reducing equivalents across the mitochondrial membrane. Fourth, tetrahydrobiopterin is more readily available for NO production and aromatic AA hydroxylation because arginine and phenylalanine boost GTP cyclohydrolase-I expression and activity. Some AAs may exert their physiological and pathological effects via modulating the arginine-NO pathway. These AAs include taurine, lysine, glutamate, homocysteine, and asymmetric dimethylarginine. Although NO at healthy levels is essential for cell signaling, inducible NO synthase may create too much NO, which can cause oxidative damage and cell death. Additionally, arginine enhances the production of important proteins and enzymes that are crucial for lowering excess fat mass in obese animals. These include AMP-activated protein kinase and peroxisome proliferator-activated receptor γ coactivator-1a, among others. In the same way, glutamine prevents intestinal atrophy and boosts development in weanling pigs by regulating the expression of genes in the small intestine that are involved in oxidative defense, signal transduction, and protein turnover. The byproducts of cysteine breakdown, known as H2S, and heme degradation, known as CO, may potentially have signaling functions in food metabolism, such as promoting the oxidation of fatty acids and glucose. Sixth, the amino acids histidine, glycine, serine, and methionine all play an important role in one-carbon metabolism, which controls gene expression and protein biological activity via methylation of DNA and proteins. Seventh, the cell's primary antioxidant and regulator of free radical homeostasis is glutathione, which is made up of cysteine, glutamate, and glycine. Finally, in response to dietary and physiological demands, the production of arginine, proline, and glutathione occurs, and the availability of glutamine for renal ammonia genesis is maximized by the coordination of AA metabolism among immune cells, skeletal muscle, the gut, and the liver.

Inter-organ metabolism of amino acids. (Wu G., 2009)

(4) Intracellular protein turnover

Protein homeostasis in tissues is dictated by intracellular protein turnover, the constant process of protein synthesis and breakdown in cells. For adults, 20-25% of their total energy expenditure goes toward protein turnover, which is a significant amount of ATP. Protein homeostasis, cell turnover, anti-aging and damage protein removal, heat-shock and immunological protein synthesis, gluconeogenesis, wound healing, tissue repair, adaptation to nutritional and pathological changes, and immune responses are all essential metabolic processes that this expensive cycle must carry out.

Incubated skeletal muscle and perfused liver both exhibit leucine's inhibitory effects on protein breakdown. Also, in both lab and live animal studies, leucine was shown to promote protein synthesis in muscles. Following reports from intestinal epithelial cells, it is possible that the underlying processes include stimulation of mTOR signaling in liver and muscle cells to block autophagy, a critical stage in lysosomal proteolysis, and promote translation start. Isoleucine and valine, the other two BCAAs, do not influence mTOR phosphorylation or muscle protein turnover, suggesting that leucine has structural specificity in cell signaling and function. Interestingly, juvenile rats did not experience any increased body size or muscle protein accretion when given leucine as a supplement to their food on a long-term basis. Similarly, 4-week-old piglets' feed intake and daily weight growth were unaffected by adding 1, 2, or 4% leucine to a corn-and soybean-based diet for 16 days. A BCAA imbalance in the blood and diet might be the consequence of using leucine supplements alone. So, to get leucine's full potential in boosting muscle building, it may be needed to take all three BCAA dietary supplements at the same time.

Under many catabolic states linked to negative protein balance in skeletal muscle, such as injury, sepsis, and lactation, there is a significant drop in intramuscular glutamine levels. These results raise the possibility of a connection between this AA and the turnover of proteins. Rennie and colleagues provided evidence that this may be the case by showing that injecting glutamine into the skeletal muscles of rats enhanced protein synthesis while decreasing protein breakdown. After that, Wu and Thompson discovered that cultured chicken skeletal muscle showed a dose-dependent increase in protein synthesis and a reduction in protein breakdown when the extracellular glutamine concentration was raised from 1 mM (the physiological level in chick plasma) to 15 mM. Although there is a paucity of direct in vivo data, a favorable correlation between intramuscular glutamine concentrations and muscle protein synthesis in chickens has been seen. Glutamate increases protein synthesis in skeletal muscle and inhibits proteolysis in small intestine mucosal cells, among other places. We don't know what's causing it, although it might be related to mTOR signaling events like in cardiac myocytes. The positive impact of L-glutamine supplementation on growth performance and prevention of intestinal atrophy in early weaned pigs may be attributable, in part, to activation of the mTOR signaling system. Since glutamine may be synthesized in animal tissues from leucine, isoleucine, and valine, it is possible that glutamine mediates the anabolic impact of BCAA in animals. Since the lactating mammary gland generates more glutamine than it absorbs from the arterial blood, this impact is probably crucial for it. Another important source of circulating glutamine in the fetus is the degradation of BCAAs in the placenta, which leads to glutamine synthesis and its release into the fetal circulation.

References

1. S Maloy. Brenner's encyclopedia of genetics, Academic Press, 2013.
2. Costa D., et al., Adsorption and self-assembly of bio-organic molecules at model surfaces: A route towards increased complexity, Surface Science Reports, 2015, 70(4): 449-553.
3. Kaur R., et al., Identification and functional annotation of expressed sequencetags based SSR markers of Stevia rebaudiana, Turkish Journal of Agriculture and Forestry, 2015, 39(3): 439-450.
4. Amaya-Farfan J., et al., AMINO ACIDS | Properties and Occurrence [M]//CABALLERO B. Encyclopedia of Food Sciences and Nutrition (Second Edition). Oxford; Academic Press. 2003: 181-92
5. Milne P J., et al., The properties, formation, and biological activity of 2, 5-diketopiperazines, 2010.
6. Li P., et al., Amino acids and immune function, British Journal of Nutrition, 2007, 98(2): 237-252.
7. Dalangin R., et al., The role of amino acids in neurotransmission and fluorescent tools for their detection, International journal of molecular sciences, 2020, 21(17): 6197.
8. Wu G. Amino acids: metabolism, functions, and nutrition, Amino acids, 2009, 37: 1-17.