Disulfide bonds, in keratins

Permanent waves. The shape of hair is determined in part by the pattern of disulfide bonds in keratin, its major protein. How can curls be induced ... 

The cleavage of the disulfide bond in keratin fibers (I) by mercaptans (II) is a reversible equilibrium reaction summarized by Equation A, where the K substituent represents keratin. 

Setting of wool and hair by either steam or hot alkaline solutions is a very old technique [54]. Steam is also very effective for producing a permanent set. Alkali and steam are known to cleave the disulfide bond in keratins [55-57] and alkaline treatments are reputed to be the most effective hair-straightening compositions because they provide the most permanent set (see the section on hair straightening in this chapter). The reaction with hydroxide is summarized by Equation E. Because sulfenic acids are generally unstable species [58], they have been suggested as intermediates that can react with the nucleophilic side chains in the keratin macromolecules [56]. 

Salts of hydrogen cyanide have also been found to be capable of nucleophilic cleavage of the disulfide bond in keratin fibers [72]. In addition, nearly quantitative conversion of cystinyl residues to lanthionyl residues can be achieved in this reaction [73]. The most plausible mechanism is given in Equations G and H [65]. This mechanism consists of two nucleophilic displacement reactions the first by cyanide on sulfur and the second by mercaptide ion on carbon. The following mechanism is consistent with the observed formation of thioether from the reaction of N-(mercaptomethyl)polyhexamethyleneadipamide disulfide (XV) with cyanide, but not with alkali [65]. 

The previous section described various reagents that have been used for the reduction of the disulfide bond in keratin fibers. Most of these reactions produce cysteinyl residues, or mercaptan groups in the fibers. 

Higher concentrations of mercaptan, higher pH [43], and higher solution-to-hair ratios all produce more extensive reduction [42,44] and ultimately more tensile damage. The decrease in dry tensile properties is less than in the wet state. This is in agreement with the work of Harris and Brown [37], who showed that up to 60% elimination of disulfide bonds in keratin fibers, by reduction and methylation, produces only small effects on the dry tensile properties (65% RH). However, the wet tensile properties decrease almost linearly with the disulfide content. 

Cystine, which contains a disulfide bond, is reported to be the most numerous and reactive amino acid present in hair keratin. Disulfide bonds in cystine are reduced by mercaptans and phosphines, and oxidized by perborates, bromates, and bleach. These reactions result in structural rearrangements within keratin which may affect the physiochemical properties of hair, since disulfide bonds in cystine contribute to the stability of hair. For example, hydrogen peroxide bleaching of hair is an oxidative process which occurs readily in an alkaline medium. This results in the formation of perhydroxy anions which have been proposed to react with cystine to form cysteic acid residues. The process of bleaching results in the loss of approximately 15% of the cystine bonds originally present in keratin and may explain the increased permeability of bleached hair to chemicals. - ... 

The curves relating residual disulfide of /S-methylated fibers and strain at the end of the yield region are identical within experimental error for a number of different keratin fibers. This suggests that disulfide bonds in both high-sulfur and low-sulfur proteins contribute to the properties of the fiber in the post-yield region. 

Menkes syndrome is linked to a copper deficiency resulting in abnormal keratinization [167]. In this genetic disorder, the kinky hair symptomatic of this disease results from an unusually high mercaptan level of cysteine, wherein only about 50% of the cysteine is oxidized to disulfide bonds during keratinization. 

Parbhu AN, Bryson WG, Lai R (1999) Disulfide bonds in the outer layer of keratin fibers confer higher mechanical rigidity correlative nano-indentation and elasticity measurement with an AFM. Biochemistry 38(36) 11755-11761... 

They are insoluble because the peptide chains are linked by disulfide bonds. Many keratins contain coils of a-helixes. Some keratines, however, were found to consist of complicated j -helical structures. This apparently has not been fully explained. Wool keratin was shown to range in molecular weight from 8,000-80,000. The extensibility of a-keratins is believed to be due to the helical structures. The extent of keratin hardness (in claws, horns, and nails) is believed to be due to the amount of sulfur links. 

Many approaches are employed to extract KRs from hair or wool fibers. These methods are based on oxidative and reductive chemistries and have been published since the early 1900s. Keratoses and kerateines represent oxidized and reduced keratin derivatives, respectively, and they have been used to prepare materials for medical applications, such as wound healing, bone regeneration, hemostasis, and peripheral nerve repair (Hill et al., 2010]. The use of either oxidative or reductive extraction techniques can lead to different mechanical properties due to the absence or presence of disulfide bonds in the material, respectively. 

Cysteine disulfide formation is one of the most important posttranslational modifications involved in protein structure. Disulfides play a crucial role in maintaining the structure of many proteins including insulin, keratin, and many other structurally important proteins. While the cytoplasm and nucleus are reducing microenvironments, the Golgi and other organelles can have oxidizing environments and process proteins to contain disulfide bonds (Scheme 5). 

Similar keratin filaments are found in hair. In a single wool fiber with a diameter of about 20 pm, millions of filaments are bundled together within dead cells. The individual keratin helices are cross-linked and stabilized by numerous disulfide bonds (see p. 72). This fact is exploited in the perming of hair. Initially, the disulfide bonds of hair keratin are disrupted by reduction with thiol compounds (see p. 8). The hair is then styled in the desired shape and heat-dried. In the process, new disulfide bonds are formed by oxidation, which maintain the hairstyle for some time. 

The strength of fibrous proteins is enhanced by covalent cross-links between polypeptide chains within the multihelical ropes and between adjacent chains in a supramolecular assembly. In a-keratins, the cross-links stabilizing quaternary structure are disulfide bonds (Box 4-2). In the hardest and toughest a-keratins, such as those of rhinoceros horn, up to 18% of the residues are cysteines involved in disulfide bonds. 

---