Prolyl and lysyl hydroxylase (P4H (for Prolyl 4-hydroxylase), LH (for Lysyl hydroxylase))

Prolyl and lysyl hydroxylases are non-heme iron-dependent dioxygenase enzymes central to collagen biosynthesis, catalyzing the incorporation of oxygen into specific proline and lysine residues in procollagen molecules. This hydroxylation is essential for the triple helix stability and subsequent cross-linking and glycosylation of collagen, impacting the formation of healthy connective tissue throughout the body. Genetic mutations or deficiencies in these enzymes, or their cofactors (such as vitamin C), result in various connective tissue diseases, while increased activity is linked to fibrosis and cancer metastasis. Some isoforms (notably LH3) also mediate glycosylation of hydroxylysine residues. Their unique specificity, cofactor dependence (including Fe^2+ and ascorbic acid), and molecular diversity make them important therapeutic and diagnostic targets in medicine.

Other names

Procollagen-proline dioxygenaseProlyl 4-hydroxylase (P4H)Procollagen-lysine 5-dioxygenaseLysyl hydroxylase (LH)LH1/PLOD1LH2/PLOD2LH3/PLOD3

Drugs or molecules that inhibit prolyl or lysyl hydroxylases would block post-translational hydroxylation of collagen, leading to less stable collagen, reduced extracellular matrix cross-linking, and possibly altered tumor microenvironment. Vitamin C deficiency inhibits hydroxylase activity, leading to disease (scurvy).