Although the other common amino acids are used as buffers, cysteine is rarely used for this purpose. Why?

Cysteine is one of the 20 standard amino acids that serve as the building blocks for proteins. It plays a critical role in biochemistry due to its unique sulfur-containing side chain, known as a thiol group. Unlike other amino acids, cysteine has the ability to form disulfide bridges, which are strong covalent bonds between the sulfur atoms of cysteine residues. These bridges are crucial in stabilizing the three-dimensional structure of proteins.

On the molecular level, cysteine's thiol group (–SH) can ionize by losing a hydrogen atom to become a thiolate anion (–S⁻). This ionization contributes to its chemical reactivity, particularly in redox reactions where it can both donate and accept electrons. The distinctive properties of the thiol group are why cysteine can engage in processes like the formation of disulfide bonds, which can impact protein folding and function.

Cysteine's ionization state is determined by its pKa value, which is approximately 8.3. Since this is above the physiological pH of 7.4, cysteine is more commonly found in its deprotonated form in the human body. The specific pKa value of the thiol group means that it is less likely to accept protons and serve as a buffer in physiological conditions.

The thiol group present in cysteine is one of the most reactive groups found in amino acids. Its reactivity is central to its biological roles, especially in the context of redox reactions. Thiol groups can participate in various chemical reactions including forming and breaking disulfide bonds, which are vital for the structure and stabilization of proteins. Disulfide bonds occur when two thiol groups oxidize to form a linkage that contributes to the protein's tertiary or quaternary structure.

The reactivity of the thiol group stems from its ability to exist in two states: the reduced thiol (–SH) and the oxidized disulfide (–S–S–). The interconversion between these states can act as a regulatory mechanism in cellular processes. For example, the redox status of thiols can influence enzyme activity, signal transduction, and gene expression.

Moreover, the highly reactive nature of cysteine's thiol makes it susceptible to oxidation, which is why it is less favored as a buffering agent. At physiological pH, the thiolate anion (–S⁻) is not inclined to mop up excess hydrogen ions. Hence, its buffering capacity is limited, and its involvement in other biological roles takes precedence over its use as a buffer in the body.

Proteins are complex molecules that play essential roles in nearly all biological processes. The structure of a protein is intricately linked to its function, often dictating how it interacts with other molecules and how it performs its biological activity. Proteins have four levels of structure: primary (the sequence of amino acids), secondary (local structures like alpha-helices and beta-sheets), tertiary (the overall 3D shapeof a single polypeptide), and quaternary (the arrangement of multiple polypeptide subunits).

Cysteine residues have a substantial effect on the tertiary and quaternary structures due to their ability to form disulfide bonds. These bonds act like molecular 'glue' that helps stabilize the folded structure of a protein, which is necessary for its biological function. In enzymes, for instance, the active site's configuration – crucial for substrate binding and catalysis – is often maintained by disulfide bonds. Alterations in these bonds can lead to a misfolded protein with reduced or lost functionality.

Because the thiol group in cysteine can impact protein structure through disulfide bond formation, its role goes beyond mere participation in peptide chains. Cysteine's reactivity is a double-edged sword; it is vital for the structural integrity of proteins but also makes it less suitable as a buffer, as this could result in unintended structural changes, potentially affecting protein function.