Hydroxylysinresten

Hydroxylysine residues are post-translationally modified lysine residues found primarily in collagen and other extracellular matrix proteins. They arise when specific lysine residues are hydroxylated by lysyl hydroxylases in the endoplasmic reticulum, a reaction that requires iron, alpha-ketoglutarate, molecular oxygen, and ascorbate as a cofactor. In collagen, hydroxylysine can be further glycosylated to form galactosylhydroxylysine and glucosylgalactosylhydroxylysine.

Hydroxylysine residues serve as anchors for cross-link formation via lysyl oxidase, enabling covalent cross-links that stabilize collagen fibrils. They also influence the binding of proteoglycans and collagen-modifying enzymes, contributing to the structural and functional properties of the extracellular matrix. The pattern and extent of hydroxylysination vary among tissue types and collagen isoforms, affecting matrix stiffness and integrity.

Clinical relevance includes defects in the enzymes that hydroxylate lysine (such as PLOD1 and PLOD2) or in the downstream cross-linking pathways, which can lead to connective tissue disorders with altered collagen stability. Vitamin C deficiency impairs hydroxylation, contributing to the brittle collagen characteristic of scurvy.

Analytical detection of hydroxylysine residues can be performed by studying collagen hydrolysates using amino acid analysis, high-performance liquid chromatography, or mass spectrometry. Overall, hydroxylysine residues are a key post-translational modification linking collagen maturation to extracellular matrix stability and tissue function.