Homocysteine in Protein Structure and Function and Human Disease

Dear Colleagues,

Homocysteine (Hcy) links two key metabolic pathways: the one-carbon/folate cycle, which provides one-carbon units for nucleotide and amino acid biosynthesis, and sulfur–amino acid metabolism, which regenerates methionine (Met) and provides cysteine (Cys). While Met and Cys are genetically encoded proteinogenic amino acids, Hcy is non-proteinogenic; however, although Hcy is not genetically encoded, proteins in our body have Hcy residues linked to lysine (Lys) residues via iso-peptide bonds (formed in a chemical reaction with Hcy-thiolactone, i.e., N-homocysteinylation) or to cysteine residues via disulfide bonds (S-homocysteinylation).

Proteins also contain Hcy bound by a peptide bond within the polypeptide chain. Such homocysteinylated proteins are formed either post-translationally via a copper/iron-dependent demethylation of Met residues or via a nitric-oxide-dependent translational mechanism on ribosomes, in which S-NO-Hcy substitutes for Met. Accumulating evidence suggests that N-Hcy-protein can promote cancer, diabetes, cardiovascular disease/stroke, neurodegenerative diseases, infertility, and pregnancy complications.

This Special Issue of the IJMS, entitled “Homocysteine in Protein Structure and Function and Human Disease”, will include a selection of original research papers and reviews on the molecular/cellular biology and pathophysiology of Hcy metabolites. Papers describing recent studies on N-Hcy-protein chemical biology and on the dysregulation of fundamental biological processes, such as mTOR signaling, autophagy, amyloid precursor protein processing, and others, due to N-Hcy-protein/Hcy-thiolactone/Hcy are welcomed.

Prof. Dr. Hieronim Jakubowski
Guest Editor

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