The Hydroxyproline-Glycine Pathway for Glycine Synthesis in Neonatal Pigs

Glycine has crucial roles in nutrition and metabolism and is the most abundant AA in the plasma of newborn pigs (~1 mM; 2- to 3-fold greater concentrations than in plasma of other species). Quantitative analysis has shown that the classic pathways for glycine synthesis (from serine, threonine, and choline) are insufficient to meet the metabolic requirements of neonatal pigs. Thus, we hypothesized that there is an additional pathway for endogenous synthesis of glycine. On d 1, 7, 14 and 21 of lactation, milk samples were obtained from 6 sows. Six piglets were euthanized on each of those days to obtain plasma and tissue samples for analyses of amino acids, enzyme activities, and expression of proteins and mRNAs. Data were analyzed by one-way ANOVA. Our results indicated high concentrations of hydroxyproline as a tripeptide in sow’s milk and plasma from piglets. The specific activities of hydroxyproline oxidase (OH-POX), alanine:glyoxylate aminotransferase (AGT), and 4-hydroxy-2-oxoglutarate aldolase (HOG), which are key enzymes for synthesis of glycine from hydroxyproline, decreased (P < 0.05) in liver and kidneys between d 1 and 21, but increased (P < 0.05) in the pancreas and small intestine. Similar results were obtained for the expression of mRNAs for those enzymes and for proline oxidase (POX). For the serine- and threonine-dependent glycine pathways, specific activities and expression of mRNAs for serine hydroxymethyltransferase (SHMT) and threonine dehydrogenase (TDH) increased (P < 0.05) between d 1 and 21. Immunohistochemistry (IHC) revealed that the localization of OH-POX and POX proteins in liver switched from periportal to perivenous hepatocytes with age, which indicated a change in hepatic catabolism of hydroxyproline and proline. In the kidneys, the abundance of OH-POX and POX proteins appeared to decrease with age. Results of IHC also revealed the presence of OH-POX and POX in the pancreas, small intestine, stomach, skeletal muscle, and gallbladder. These findings indicate the presence of the hydroxyproline-glycine pathway for the synthesis of glycine from milk- and endogenous collagen-derived hydroxyproline via interorgan metabolism in neonatal pigs which may compensate for a severe deficiency of glycine in sow’s milk. Supported by funds from USDA-NIFA.