Cysteine: Definition, Structure, Benefits, Sources and Uses

Cysteine is a conditionally essential amino acid important for numerous biological functions because of its distinctive thiol (-SH) group, which enhances protein stability by forming disulfide bonds. It is also a precursor for glutathione, a crucial antioxidant that defends cells against oxidative stress. This amino acid is naturally present in foods like poultry, eggs, and legumes, and it can also be synthesized biologically or manufactured industrially for use in pharmaceuticals, cosmetics, and food additives.

What is Cysteine?

Cysteine (Cys or C) is a semi-essential proteinogenic amino acid, whose thiol side chain commonly acts as a nucleophile in enzymatic reactions. Like other amino acids, cysteine exists as a zwitterion. Based on its homology to D- and L-glyceraldehyde, cysteine has L-chirality in the older D/L labeling system. In the newer R/S chirality naming system, cysteine is designated as R-chiral due to the presence of sulfur as the second neighbor to the asymmetric carbon atom. Most other chiral amino acids have lighter atoms at that position and exhibit S-chirality. The unique properties of cysteine's thiol group at the molecular end make it active in many different physiological contexts. Thiol compounds not only help protect sensitive tissues from oxidation but also assist the body in detoxifying harmful chemicals and carcinogens, rendering them harmless. Therefore, cysteine is primarily used in medicine, cosmetics, biochemical research, and related fields.

Cysteine Amino Acid

Non-natural derivatives of cysteine have been synthesized to harness the core properties of this amino acid, often modifying its structure to enhance stability, reactivity, or bioavailability. These derivatives are essential in various fields, such as pharmaceuticals, biotechnology, and material sciences, due to their adaptability and functional diversity. For example, n-acetylcysteine (NAC) is a derivative of cysteine where an acetyl group is attached to the nitrogen atom. This modification improves its bioavailability, making it a more effective supplement for replenishing cysteine and promoting the synthesis of glutathione, a critical intracellular antioxidant.

Cysteine Structure

The basic chemical structure of cysteine includes an amino group, nitrogen, carbon, oxygen, hydrogen, and a sulfur-containing thiol group. Its molecular formula is C₃H₇NO₂S. Cysteine is an isomer of cystine and can be derived from methionine. It is a white crystalline or crystalline powder, soluble in water, slightly odorous, and poorly soluble in ethanol and ether. Its melting point is 240 °C, and it belongs to the monoclinic crystal system. Cysteine can form insoluble thiol salts (mercaptides) with metal ions such as Ag⁺, Hg⁺, and Cu⁺. Additionally, cysteine is stable in acidic conditions but easily oxidized to cystine in neutral and alkaline solutions.

Fig. 1. Structure of cysteine.

Cysteine has traditionally been considered a hydrophilic amino acid, mainly due to the chemical parallelism between its thiol group and the hydroxyl group on the side chains of other polar amino acids. However, cysteine's side chain has been shown to stabilize hydrophobic interactions in micelles more effectively than the side chains of non-polar glycine or polar serine. Statistical analyses of amino acid occurrence in different chemical environments within protein structures have shown that free cysteine residues are often associated with hydrophobic regions of proteins. The hydrophobicity of cysteine is comparable to that of known non-polar amino acids such as methionine and tyrosine (tyrosine is a polar aromatic amino acid but also hydrophobic). This hydrophobicity is far greater than that of known polar amino acids such as serine and threonine. In hydrophobicity scales, which rank amino acids from most hydrophobic to most hydrophilic, cysteine consistently appears on the hydrophobic end of the spectrum, even in methods that are unaffected by the tendency of cysteine to form disulfide bonds in proteins. Thus, cysteine is now often classified as a hydrophobic amino acid, although sometimes it is categorized as mildly polar or polar.

Cysteine Benefits

The thiol group of cysteine is nucleophilic and easily oxidized. When the thiol is ionized, its reactivity increases, and since the pKa of cysteine residues in proteins is near neutral, they often participate in biochemical reactions in their thiolate form within cells. Due to its high reactivity, one of the most important functions of cysteine is as a free radical scavenger, antioxidant, chelator of circulating copper, and general metabolic enhancer.

• Precursor to Glutathione: Cysteine and cysteine residues possess antioxidant properties due to the redox capabilities of the thiol group. This antioxidant activity is often expressed in the tripeptide glutathione, which is present in humans and other organisms. The systemic bioavailability of orally ingested glutathione (GSH) is negligible. Therefore, it must be biosynthesized from its constituent amino acids—cysteine, glycine, and glutamic acid. Since nitrogen from amino groups is recycled through glutamic acid as an intermediate, glutamic acid is usually sufficient, but supplementation of cysteine and glycine in the diet can enhance glutathione synthesis.
• Binding Metal Ions: Aside from iron-sulfur proteins, many other metal cofactors in enzymes are coordinated by the thiolate groups of cysteine residues. Examples include zinc in zinc finger proteins and alcohol dehydrogenase, copper in plastocyanin, iron in cytochrome P450, and nickel in [NiFe]-hydrogenase. Thiol groups also have a high affinity for heavy metals, so cysteine-containing proteins like metallothioneins tightly bind metals such as mercury, lead, and cadmium.
• Detoxifying Agent: Cysteine functions as a detoxifying agent, eliminating more toxins from the body than any other substance. During the process of detoxifying cytotoxins, cysteine may be temporarily converted into N-acetylcysteine, which is considered an intermediary in cysteine's detoxification mechanism. Therefore, it is commonly used in emergency rooms to counteract overdoses of toxic substances, such as acetaminophen.
• Protein Structure and Stability: Cysteine is encoded by the UGU and UGC codons during the translation of messenger RNA into polypeptides. Cysteine is crucial for protein folding due to its structural role. Its thiol group creates disulfide bonds, which are essential for stabilizing proteins' three-dimensional structures, particularly in enzymes and antibodies.

Cysteine Sources

The multifunctionality and wide-ranging applications of cysteine have made its sources a critical research topic across various fields. Cysteine can be categorized into three main sources: dietary sources, biosynthesis, and industrial sources (including non-natural derivatives). A thorough understanding of these sources is essential for its applications in biomedicine, the food industry, and pharmaceuticals, particularly in areas such as nutritional supplementation, disease treatment, and industrial production.

• Dietary Sources

Cysteine is categorized as a semi-essential amino acid in relation to dietary sources. Although the body has the ability to produce it, there are specific circumstances—like during growth phases, recovery from injuries, or illness—when supplementary intake from food becomes necessary to fulfill the body's requirements. Cysteine is primarily sourced from protein-rich foods, with meats such as chicken, beef, and pork offering substantial amounts. These animal proteins are decomposed by the digestive system into amino acids, including cysteine, for the body's use. Additionally, cysteine can be found in eggs and dairy products like cheese and milk, which offer high-quality protein and help maintain adequate cysteine levels in the body.

• Cysteine Biosynthesis

In animals, the production of cysteine begins with the amino acid serine. Methionine contributes sulfur by being transformed into homocysteine via S-adenosylmethionine. The enzyme cystathionine β-synthase then links homocysteine and serine to form the asymmetrical thioether, cystathionine. Following this, cystathionine γ-lyase splits cystathionine into cysteine and α-ketobutyrate. In plants and bacteria, cysteine formation also initiates with serine, which is altered into O-acetylserine by the action of serine acetyltransferase. Cysteine synthase subsequently employs a sulfide source to convert this ester into cysteine, while releasing acetate in the process.

• Industrial Synthesis

In addition to biosynthesis and dietary intake, cysteine can also be synthesized through industrial processes, particularly to meet the demands of the pharmaceutical, food processing, and cosmetics industries. Industrial cysteine synthesis involves two main methods: natural extraction and chemical synthesis.

• Natural Extraction: Early industrial methods involved extracting cysteine from animal sources, typically by acid hydrolysis of feathers or hair. While this method can produce high-purity cysteine, the process is complex and requires large quantities of raw materials.
• Fermentation: With advancements in biotechnology, microbial fermentation has become a common method for industrial cysteine production. Engineered bacteria, such as E. coli, are used to ferment specific carbon sources, with metabolic pathways controlled to produce large quantities of cysteine. This method is not only efficient but also environmentally friendly and cost-effective.
• Chemical Synthesis and Non-Natural Derivatives: Chemical synthesis of cysteine involves using petrochemical raw materials or other chemical pathways. Through chemical modification, cysteine can also be derived into many non-natural forms, which are particularly important in the pharmaceutical industry. For example, NAC is a significant cysteine derivative widely used as an antioxidant and mucolytic agent.

What Does Cysteine Do?

The diverse chemical properties of cysteine and its derivatives make them valuable across a wide range of industries. From pharmaceuticals to cosmetics and food technology, cysteine's versatility has led to its widespread application.

• Pharmaceuticals

Cysteine and its derivatives are integral in drug formulations, particularly in the development of mucolytic agents like NAC and SCMC for respiratory conditions. Additionally, cysteine's role in glutathione production makes it valuable in treatments aimed at reducing oxidative stress-related diseases, including liver disorders and neurodegenerative conditions. NAC is also being investigated in clinical trials for its potential in treating mental health disorders like schizophrenia and addiction, due to its ability to modulate glutamate pathways in the brain.

• Biotechnology and Protein Engineering

Cysteine's thiol group is critical for engineering proteins with tailored disulfide bonds, enhancing stability and function. It is commonly used in bioconjugation strategies, including antibody-drug conjugates (ADCs), where cysteine residues are selectively modified to attach therapeutic agents. Non-natural cysteine derivatives, such as PEGylated cysteine, are used to improve the pharmacokinetics and stability of therapeutic proteins and peptides by extending their half-life in the bloodstream.

• Cosmetics and Personal Care

In the cosmetics industry, cysteine derivatives like cysteamine and NAC are used in formulations for their antioxidant, anti-aging, and skin-brightening properties. These compounds help reduce oxidative stress on the skin and promote cellular repair, making them popular in anti-wrinkle creams and treatments for hyperpigmentation. Cysteine itself is used in hair care products due to its role in keratin synthesis, improving hair strength and shine.

• Food and Agriculture

Cysteine is used in the food industry as a dough conditioner and flavor enhancer. Its derivatives can also be used in animal feed to improve the nutritional value and health of livestock, particularly in promoting growth and improving immune response.

** Recommended Products **

Online Inquiry

Name *

Email *

Phone *

Services & Products of Interest * Cysteine: Definition, Structure, Benefits, Sources and Uses

Project Description

Quantity *

- mg g kg ton

Verification Code *

SUBMIT