Research Article: Demethylation of methionine and keratin damage in human hair

Date Published: February 26, 2018

Publisher: Springer Vienna

Author(s): Kamila Borowczyk, Joanna Suliburska, Hieronim Jakubowski.


Growing human head hair contains a history of keratin and provides a unique model for studies of protein damage. Here, we examined mechanism of homocysteine (Hcy) accumulation and keratin damage in human hair. We found that the content of Hcy-keratin increased along the hair fiber, with levels 5–10-fold higher levels in older sections at the hair’s tip than in younger sections at hair’s base. The accumulation of Hcy led to a complete loss of keratin solubility in sodium dodecyl sulfate. The increase in Hcy-keratin was accompanied by a decrease in methionine-keratin. Levels of Hcy-keratin were correlated with hair copper and iron in older hair. These relationships were recapitulated in model experiments in vitro, in which Hcy generation from Met exhibited a similar dependence on copper or iron. Taken together, these findings suggest that Hcy-keratin accumulation is due to copper/iron-catalyzed demethylation of methionine residues and contributes to keratin damage in human hair.

Partial Text

Homocysteine (Hcy) is a universal intermediate in the metabolism of two major sulfur-containing amino acids methionine (Met) and cysteine. While Met and cysteine (Cys) are canonical coded amino acids that are incorporated into proteins by the ribosomal biosynthetic apparatus, Hcy is not (Jakubowski 2017). However, although Hcy is a non‐coded amino acid, proteins carry Hcy residues linked via an isopeptide bond to lysine (Lys) residues (N-Hcy-protein) (Jakubowski 1999, 2002; Sikora et al. 2014) or via a disulfide bond to cysteine residues (S-Hcy-protein) (Lim et al. 2003; Jacovina et al. 2009). Proteins can also carry Hcy bound by a peptide bond than can be formed translationally by a nitric oxide-dependent mechanism (Jakubowski 2000a, b, 2001, 2017) or post-translationally by metal-dependent demethylation of a protein methionine residue (Mozziconacci et al. 2013). However, although about a dozen individual proteins that contain Hcy N-linked to lysine residues or S-linked to cysteine residues have been identified in vivo in humans or animals (Jakubowski 2013), proteins that carry Hcy bound by a peptide bond have not yet been identified.

The present work shows that older sections of growing human hair accumulate Hcy-keratin with a concomitant reduction of Met-keratin levels. Our data are consistent with the mechanism of Hcy-keratin accumulation involving Cu- and Fe-dependent demethylation of Met residues in keratin. We also show that this process is associated with hair keratin damage, manifested by a loss of solubility in SDS solutions. To the best of our knowledge this is the first example of Cu/Fe-dependent protein Met → Hcy conversion associated with protein damage in humans.




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