Hydroxyproline in animal metabolism, nutrition, and cell signaling. Academic Article uri icon


  • trans-4-Hydroxy-L-proline is highly abundant in collagen (accounting for about one-third of body proteins in humans and other animals). This imino acid (loosely called amino acid) and its minor analogue trans-3-hydroxy-L-proline in their ratio of approximately 100:1 are formed from the post-translational hydroxylation of proteins (primarily collagen and, to a much lesser extent, non-collagen proteins). Besides their structural and physiological significance in the connective tissue, both trans-4-hydroxy-L-proline and trans-3-hydroxy-L-proline can scavenge reactive oxygen species and have both structural and physiological significance in animals. The formation of trans-4-hydroxy-L-proline residues in protein kinases B and DYRK1A, eukaryotic elongation factor 2 activity, and hypoxia-inducible transcription factor plays an important role in regulating their phosphorylation and catalytic activation as well as cell signaling in animal cells. These biochemical events contribute to the modulation of cell metabolism, growth, development, responses to nutritional and physiological changes (e.g., dietary protein intake and hypoxia), and survival. Milk, meat, skin hydrolysates, and blood, as well as whole-body collagen degradation provide a large amount of trans-4-hydroxy-L-proline. In animals, most (nearly 90%) of the collagen-derived trans-4-hydroxy-L-proline is catabolized to glycine via the trans-4-hydroxy-L-proline oxidase pathway, and trans-3-hydroxy-L-proline is degraded via the trans-3-hydroxy-L-proline dehydratase pathway to ornithine and glutamate, thereby conserving dietary and endogenously synthesized proline and arginine. Supplementing trans-4-hydroxy-L-proline or its small peptides to plant-based diets can alleviate oxidative stress, while increasing collagen synthesis and accretion in the body. New knowledge of hydroxyproline biochemistry and nutrition aids in improving the growth, health and well-being of humans and other animals.

published proceedings

  • Amino Acids

altmetric score

  • 0.5

author list (cited authors)

  • Hu, S., He, W., & Wu, G.

citation count

  • 15

complete list of authors

  • Hu, Shengdi||He, Wenliang||Wu, Guoyao

publication date

  • April 2022