Classification and Application of Natural Amino Acids

The basic building blocks of oligopeptide and peptide drugs are amino acids. There are 20 naturally occurring amino acids that form the fundamental structure of proteins. These can be categorized into nonpolar amino acids (hydrophobic amino acids), polar uncharged amino acids (hydrophilic amino acids), basic amino acids (polar positively charged amino acids), and acidic amino acids (polar negatively charged amino acids).

Classification of Amino Acids

Below is a summary of the structures, classifications, and primary physiological roles of the common naturally occurring amino acids that constitute proteins. The polarity or hydrophobicity/hydrophilicity described here does not refer to the physical and chemical properties of the entire amino acid molecule but rather to its side chain (R-group). If the R-group consists solely of hydrogen (H) or carbon and hydrogen (C, H), the amino acid is nonpolar and hydrophobic. If it contains polar side chains such as -OH, -SH, -COOH, or -NH2, the amino acid is classified as polar and hydrophilic.

Nonpolar Amino Acids (9): Glycine, Alanine, Phenylalanine, Leucine, Isoleucine, Proline, Valine, Tryptophan, Methionine (Methionine)

Polar Uncharged Amino Acids (6): Serine, Tyrosine, Threonine, Cysteine, Glutamine, Asparagine

Basic Amino Acids (3): Histidine, Lysine, Arginine

Acidic Amino Acids (2): Aspartic Acid, Glutamic Acid

In recent years, researchers have identified the 21st and 22nd standard amino acids in some proteins: selenocysteine and pyrrolysine. The 22nd amino acid, pyrrolysine, is found only in archaea and certain bacteria. Therefore, there are 21 natural amino acids that form human proteins. Except for glycine, all these basic amino acids are L-configured α-amino acids and play crucial roles in sustaining life and regulating biological functions. These functions include participating in protein formation, cellular signal transduction, membrane transport, enzymatic catalysis, DNA synthesis or repair, and detoxification within the body.

There are eight essential amino acids that the human body cannot synthesize and must be obtained from food: Valine, Isoleucine, Leucine, Phenylalanine, Methionine, Tryptophan, Threonine, Lysine. Additionally, there are two semi-essential amino acids that the body synthesizes in insufficient amounts, requiring partial dietary intake, particularly for infants: Arginine and Histidine.

Now, let's explore these 22 natural amino acids and their primary biological functions.

Glycine (G or Gly) -α-Aminoacetic Acid

Glycine is one of the nonpolar α-amino acids (although some classify it as a polar uncharged amino acid, based on its R-group, it is considered nonpolar in biological contexts). It is a non-essential amino acid. Glycine is highly hydrophilic, easily soluble in water, and nearly insoluble in ethanol and ether, making it a hydrophobic amino acid. It is a component of the endogenous antioxidant glutathione and is often supplemented externally under severe physiological stress. Sometimes, it is also considered a semi-essential amino acid. Beyond protein synthesis, glycine plays roles in neurotransmission and detoxification within the body.

Alanine (A or Ala)-α-Aminopropionic Acid

One of the non-polar α-amino acids, a non-essential amino acid. It is soluble in water, but insoluble in ethanol, ether, and acetone, and is considered a hydrophobic amino acid. It has optical activity. In the body, it primarily participates in protein synthesis and energy metabolism (carbohydrate and acid metabolism).

Valine (V or Val)-β-Methyl-α-Aminobutyric Acid

One of the non-polar α-amino acids, one of the 8 essential amino acids, and one of the three branched-chain amino acids (valine, leucine, isoleucine). Soluble in water, but insoluble in ethanol, it is a hydrophobic amino acid. Valine is a glucogenic amino acid that, along with leucine (a ketogenic amino acid) and isoleucine (a mixed glucogenic and ketogenic amino acid), plays a role in the conversion of the three major nutrients (proteins, carbohydrates, and fats) through the citric acid cycle. It promotes body growth, tissue repair, regulates blood sugar, provides energy, and also participates in nitrogen clearance and the elimination of toxins from the body.

Leucine (L or Leu)-γ-Methyl-α-Aminovaleric Acid

One of the non-polar α-amino acids, one of the 8 essential amino acids, and one of the three branched-chain amino acids (valine, leucine, isoleucine). Easily soluble in formic acid, slightly soluble in water, and insoluble in ethanol, it is a hydrophobic amino acid. It participates in protein synthesis in the body, regulates blood sugar, promotes insulin secretion, and maintains blood sugar and nitrogen balance.

Isoleucine (I or Ile)-β-Methyl-α-Aminovaleric Acid

One of the non-polar α-amino acids, one of the 8 essential amino acids, and one of the three branched-chain amino acids (valine, leucine, isoleucine). Slightly soluble in water, insoluble in ethanol, it is a hydrophobic amino acid. It is involved in protein synthesis, blood sugar regulation, energy provision, nitrogen balance maintenance, and tissue growth promotion.

Phenylalanine (F or Phe)-β-Phenyl-α-Aminopropionic Acid

One of the non-polar α-amino acids, one of the 8 essential amino acids, an aromatic amino acid. Soluble in water, but insoluble in ethanol and ether, it is a hydrophobic amino acid. In the body, phenylalanine is hydroxylated by phenylalanine hydroxylase to form tyrosine, which together with tyrosine participates in the synthesis of neurotransmitters and hormones, and is involved in carbohydrate and fat metabolism.

Proline (P or Pro)-α-Carboxy-4-Pyrrolidine

One of the non-polar α-cyclic imino acids, a non-essential amino acid. Soluble in hot water and ethanol, it is a hydrophobic amino acid. In the body, proline is involved in collagen synthesis, tissue repair, enzyme catalysis, and more.

Tryptophan (W or Trp)-α-Amino-β-(3-Indolyl)Propionic Acid

One of the non-polar α-amino acids, one of the 8 essential amino acids, an aromatic amino acid. Easily soluble in formic acid, slightly soluble in water, and insoluble in ethanol, it is a hydrophobic amino acid. It is involved in plasma protein turnover and the production of neurotransmitters in the body.

Methionine (M or Met)-α-Amino-γ-Methylthiobutyric Acid

One of the non-polar α-amino acids, one of the 8 essential amino acids. Soluble in water, insoluble in ethanol and ether, it is a hydrophobic amino acid. Methionine participates in protein synthesis, the conversion of cysteine, sulfur provision, methyl group donation, and helps maintain growth and nitrogen balance in the body.

Serine (S or Ser)-α-Amino-β-Hydroxypropionic Acid

A polar α-amino acid (neutral), a non-essential amino acid. Easily soluble in water, but insoluble in ethanol, ether, and acetone, it is a hydrophilic amino acid. Serine participates in protein synthesis and signal transduction in the nervous system.

Threonine (T or Thr)-α-Amino-β-Hydroxybutyric Acid

A polar α-amino acid (neutral), one of the 8 essential amino acids. Soluble in water, insoluble in ethanol, a hydrophilic amino acid, and both glucogenic and ketogenic. In the body, threonine is involved in protein phosphorylation, promotes growth and development, and helps with water retention and moisture maintenance.

Tyrosine (Y or Tyr)-α-Amino-β-(4-Hydroxyphenyl)Propionic Acid

A polar α-amino acid (neutral), a non-essential amino acid (conditionally essential when phenylalanine is sufficient). Soluble in dilute hydrochloric acid, slightly soluble in water, and insoluble in ethanol, it is both glucogenic and ketogenic. In the body, tyrosine is involved in protein synthesis and neuronal signaling.

Cysteine (C, Cys)-α-amino-β-thiolpropanoic acid

A polar α-amino acid (non-charged), non-essential amino acid (conditionally essential, can be converted from the essential amino acid methionine). Soluble in water, insoluble in ether and acetone, a hydrophilic amino acid, and a glucogenic amino acid. It is involved in protein formation, detoxification of various toxins (such as formaldehyde, acetaldehyde, alcohol, etc.), and acts as an antioxidant to clear free radicals.

Asparagine (N, Asn)-α-amino-acylamide acid

A polar α-amino acid (non-charged), non-essential amino acid. Soluble in water, insoluble in ethanol and ether. It participates in the synthesis of glycoproteins.

Glutamine (Q, Gln)-α-amino-glutamylamide acid

A polar α-amino acid (non-charged), non-essential amino acid. Soluble in water, insoluble in ethanol and ether. It is involved in protein synthesis and DNA/RNA synthesis.

Aspartic Acid (D, Asp)-α-amino-succinic acid

One of the two acidic amino acids, non-essential amino acid. Slightly soluble in water (dissolves in boiling water), difficult to dissolve in ethanol and ether. It participates in protein formation, the ornithine cycle, and hormone regulation in the body.

Glutamic Acid (E, Glu)-α-amino-glutamic acid

One of the two acidic α-amino acids, non-essential amino acid. Easily soluble in dilute hydrochloric acid or 1 mol/L sodium hydroxide solution, dissolves in hot water, slightly soluble in water, insoluble in ethanol and ether. It participates in protein metabolism and acts as an excitatory neurotransmitter in the brain.

Histidine (H, His)-α-amino-β-(4-imidazole)propanoic acid

A basic α-amino acid, one of the two semi-essential amino acids (especially important for infants). Soluble in water, slightly soluble in ethanol, insoluble in ether. It participates in the formation of metalloproteins and enzyme catalysis in the body.

Lysine (L, Lys)-α,ε-diaminohexanoic acid

A basic α-amino acid, one of the eight essential amino acids. Easily soluble in water, slightly soluble in ethanol, insoluble in ether. It participates in protein formation, regulation of metabolic balance, and enhancement of immune function in the body.

Arginine (R, Arg)-α-amino-δ-guanidino-pentanoic acid

A basic α-amino acid, one of the two semi-essential amino acids. Easily soluble in water, slightly soluble in ethanol, insoluble in ether. It is involved in protein formation and the ornithine cycle in the body.

Selenocysteine (U, Sec)-α-amino-β-selenohydroxypropanoic acid

Selenocysteine is the most recently discovered essential natural amino acid in humans and is the main form of selenium in proteins. It is the only amino acid that contains a semi-metal element. It participates in the formation of selenoproteins in the body and is found in the active centers of 25 known selenoenzymes (such as glutathione peroxidase), exhibiting antioxidant activity.

Pyrrolysine

A basic α-amino acid, the most recently discovered essential natural amino acid, found in some methane-producing archaea and bacteria. It participates in methyltransferase catalysis.

Dissociation of Amino Acids

Amino acids are amphoteric ions, exhibiting zwitterionic dissociation properties. The dissociation mode depends on the pH of the solution.

The pKa value of α-COOH is approximately 2.0. When pH > 3.5, α-COOH exists in the form of α-COO⁻.

The pKa value of α-NH2 is approximately 9.4. When pH < 8.0, α-NH2 exists in the form of α-NH3⁺.

When the pH of the solution is between 3.5 and 8.0, amino acids exist as zwitterions.

The buffering capacity of amino acids is strongest when the solution's pH is at the pKa value.

pKa of 20 common natural amino acids

Application of Natural Amino Acids

Food Industry

Flavoring Agents: Monosodium glutamate (MSG), with glutamic acid as its main component, is a widely used umami enhancer that enhances the flavor of food. Additionally, acidic amino acids like aspartic acid and glutamic acid also have a certain sour taste and can be used as acidulants.

Nutritional Fortifiers: In food processing, natural amino acids are often added to foods to enhance their nutritional value. For example, essential amino acids such as tryptophan and phenylalanine are added to infant formula to meet the nutritional needs of infants.

Flavor Compounds: The Maillard reaction between amino acids and sugars is one of the key reasons for the generation of aroma and browning in food processing. During cooking, the decomposition and transformation of amino acids also produce compounds with special flavors, such as the aroma of roasted meat.

Pharmaceutical Industry

Pharmaceutical Processes: Amino acids can serve as solvent additives in protein purification and stabilizers in protein formulations, enhancing the long-term stability of proteins. For example, histidine and arginine are commonly used as pH buffers and stabilizers in antibody drugs and other protein formulations.

Pharmaceutical Ingredients: Amino acids themselves can be used as medicines. For instance, glutamic acid, arginine, and aspartic acid are used in the treatment of liver diseases, cardiovascular diseases, and other conditions. Moreover, some amino acid derivatives also have important medicinal value, such as L-dopa, which is used to treat Parkinson's disease.

Therapeutic Applications: Amino acids play an important role in maintaining normal physiological functions and promoting disease recovery. For example, amino acids are vital nutritional components in modern intravenous nutrition and "elemental diet" therapies, playing an active role in maintaining the nutrition of critically ill patients and saving lives.

Cosmetics Industry

Moisturizers: Amino acids have good hydrophilicity and moisturizing properties, making them useful as moisturizers in cosmetics. For example, amino acids like glycine and alanine can increase the moisture content of the skin and hair, keeping them soft and smooth.

Surfactants: Surfactants made from amino acids are gentle and non-irritating to the skin, widely used in cleansing products like facial cleansers and body washes.

Skin Repair: Some amino acids promote the regeneration and repair of skin cells and can be used to treat skin damage, acne, and other skin issues. For instance, arginine can promote collagen synthesis, enhancing the skin's elasticity and toughness.

Agriculture Industry

Animal Feed Additives: Natural amino acids can be used as nutritional additives in animal feed to improve animal growth performance and immunity. For example, adding essential amino acids like lysine and methionine to the feed of pigs, chickens, and other livestock can promote their growth and development, improving feed utilization.

Plant Growth Promoters: Some natural amino acids promote plant growth and can be used as plant growth regulators. For instance, tryptophan can be converted into auxin, regulating plant growth and development, improving crop yield and quality.