3Hydroxyproline

3-Hydroxyproline is a hydroxylated derivative of the amino acid proline. It exists in both L- and D- forms, though in human proteins the L-3-hydroxyproline isomer is the most common. It is formed by post-translational hydroxylation of proline residues in proteins, with collagen being a prominent site of modification.

In vertebrates, 3-hydroxyproline is found at selective positions within collagen and other extracellular matrix proteins and is far less abundant than 4-hydroxyproline. Its precise functional role is not as well understood as that of 4-hydroxyproline, but it is thought to contribute to local structural stabilization and to modulate protein–protein interactions in certain contexts.

The installation of the hydroxyl group at the third carbon is carried out by prolyl-3-hydroxylases, members of the 2-oxoglutarate-dependent dioxygenase family. These enzymes require iron, oxygen, and ascorbate as cofactors and act during collagen maturation in the endoplasmic reticulum. Prolyl-3-hydroxylation occurs at specific proline residues, with patterns influenced by collagen type and tissue context.

Defects in the prolyl-3-hydroxylation pathway have been linked to connective tissue disorders in some studies, indicating that precise hydroxylation patterns contribute to collagen stability. Compared with 4-hydroxyproline, 3-hydroxyproline–related pathologies are less well characterized.

Analytical detection typically involves measuring 3-hydroxyproline after acid hydrolysis of collagen, using chromatography or mass spectrometry. The isomeric forms and the position of the hydroxyl group yield multiple possibilities, with the L-3-hydroxyproline form being most common in higher organisms.