Demethylation of methionine and keratin damage in human hair

Kamila Borowczyk,Hieronim Jakubowski,Joanna Suliburska

doi:10.1007/s00726-018-2545-3

Abstract

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.

Highlights

Homocysteine (Hcy) is a universal intermediate in the metabolism of two major sulfur-containing amino acids methionine (Met) and cysteine
We found that each hair sample contained Hcy, which varied 14-fold between individuals and did not depend on individual’s age or gender (Fig. 1a)
Because keratin is the major component of hair, accounting for 95% by weight (Robbins 2012), these findings suggest that Hcy is a natural component of human hair keratin

Summary

Introduction

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). Proteins can 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). 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.

Methods

Results

Conclusion