Metabolism, Nutrition, and Redox Signaling of Hydroxyproline

Significance: Hydroxyproline is a structurally and physiologically important imino acid in animals. It is provided from diets and endogenous synthesis, and its conversion into glycine enhances the production of glutathione, DNA, heme, and protein. Furthermore, oxidation of hydroxyproline by hydroxyproline oxidase (OH-POX) plays an important role in cell antioxidative reactions, survival, and homeostasis. Understanding the mechanisms whereby hydroxyproline participates in metabolism and cell signaling can improve the nutrition and health of animals and humans. Recent Advances: Hydroxyproline is highly abundant in milk and is utilized for renal synthesis of glycine to support neonatal growth, development, and survival. The oxidation of hydroxyproline by mitochondrial OH-POX generates reactive oxygen species (ROS). Enhanced ROS production contributes to the regulation of oxidative defense, apoptosis, angiogenesis, tumorigenesis, hypoxic responses, and cell survival in animals. Critical Issues: Although dietary hydroxyproline enters the portal circulation, its utilization by the portal-drained viscera is unknown. Pathways for hydroxyproline metabolism and their regulation at the molecular, cellular, and whole-body levels remain to be defined. Furthermore, the mechanisms responsible for hydroxyproline-derived ROS and related metabolites to induce cell survival or apoptosis are unknown. Future Directions: Interorgan metabolism of hydroxyproline (including synthesis, catabolism, and flux) in animals must be quantified using isotope technologies. Efforts should also be directed toward studying dietary, hormonal, and epigenetic regulation of OH-POX expression at transcriptional and translational levels. Another emerging research need is to understand the roles of cellular redox and signaling networks involving both ROS and Δ1-pyrroline-3-hydroxy-5-carboxylate in nutrition, health, and disease.