Cysteine is a sulfur-containing amino acid, one of the molecules that form proteins. It is considered semi-essential because the human body can produce it through a process called biosynthesis. This internal construction, which occurs primarily in the liver, means cysteine does not always need to be obtained from diet. This capability distinguishes it from essential amino acids, which must be acquired exclusively from food.
The Building Blocks for Cysteine
The synthesis of cysteine begins with an essential amino acid called methionine. Since the body cannot make methionine, it must be acquired from dietary sources such as meat, fish, and dairy products. Inside the body, methionine is converted into an intermediate molecule known as homocysteine, which provides the sulfur atom for cysteine.
The pathway also requires the amino acid serine to provide the carbon backbone for the new molecule. Unlike methionine, serine is a non-essential amino acid, meaning the body can produce it on its own. The combination of homocysteine, which carries the sulfur, and serine, which provides the framework, sets the stage for the main reaction.
The Transsulfuration Pathway
The synthesis of cysteine in mammals occurs through the transsulfuration pathway, which transfers a sulfur atom from homocysteine to serine. The first step involves the enzyme cystathionine β-synthase (CBS). This enzyme chemically joins one molecule of homocysteine and one of serine to create a new, larger molecule called cystathionine.
The newly formed cystathionine serves as a temporary intermediate, holding the necessary components in place. A second enzyme, cystathionine γ-lyase (CGL), then enters to cleave this molecule at a specific point.
This enzymatic cleavage by CGL breaks cystathionine into two separate molecules. One is the desired product, cysteine, which now contains the sulfur atom originally from methionine. The other is a byproduct called alpha-ketobutyrate, which can be further metabolized by the cell.
Biological Roles of Cysteine
Cysteine performs several specialized functions, with a primary role in maintaining protein structure. The sulfur atom in cysteine allows it to form a strong covalent bond, known as a disulfide bridge, with another cysteine molecule. These bridges act like molecular staples, locking parts of a protein chain together to provide stability to structures like keratin in hair and nails.
Cysteine is also a direct precursor to the antioxidant glutathione. Glutathione neutralizes harmful reactive oxygen species, which are damaging byproducts of normal metabolism. By providing the sulfur-containing component needed to build it, cysteine is central to the body’s defense system against cellular stress. Cysteine also contributes to the synthesis of other molecules, such as taurine, which has roles in bile salt formation and cardiovascular function.
Regulation of Cysteine Production
The body regulates the production of cysteine to ensure a sufficient supply without creating a surplus, which can be toxic. Control of the transsulfuration pathway is largely dependent on the availability of its starting materials, particularly methionine. When dietary intake of methionine is high, it signals that resources are plentiful and can be directed toward the pathway.
A second layer of control involves S-adenosylmethionine (SAM), a molecule produced from methionine that indicates the cell’s methionine status. When SAM levels are high, it acts as a direct activator of the enzyme cystathionine β-synthase (CBS). This activation signals that there is enough methionine for other cellular functions and that excess can be safely channeled into producing cysteine.
Consequences of Impaired Synthesis
Failures in the cysteine synthesis pathway, often from genetic defects in the enzymes involved, can lead to serious health issues. The most documented condition is classical homocystinuria, caused by a deficiency in the cystathionine β-synthase (CBS) enzyme. Without a functional CBS enzyme, the conversion of homocysteine and serine into cystathionine is blocked, halting cysteine production.
This breakdown in the pathway leads to a significant buildup of homocysteine in the blood and urine. This accumulation is toxic and responsible for the disorder’s symptoms. Individuals with homocystinuria often experience developmental delays, skeletal abnormalities, and a high risk of blood clots and cardiovascular events. These consequences highlight the pathway’s importance in maintaining metabolic balance.