Endogenous Synthesis of Glycine from Hydroxyproline in Neonatal Pigs
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This study was conducted to test the hypothesis that hydroxyproline is a novel and major substrate for endogenous synthesis of glycine in sow-reared pigs. At 0, 7, 14, and 21 days of age, neonatal piglets with a normal or low birth weight (BW) were sacrificed, and their tissue samples were obtained for metabolic studies, activities of glycine-synthetic enzymes, mRNA expression, and the localization of proteins for those enzymes. Moreover, normal and IUGR piglets received oral administration of glycine (0.2, 0.4, and 0.8 g/kg BW) between days 0 and 14 to evaluate a role for endogenous synthesis of glycine in the growth of piglets. Results from the studies of normal birth-weight piglets demonstrated that the activities of hydroxyproline oxidase (OH-POX), proline oxidase (POX), alanine:glyoxylate transaminase (AGT), and 4-hydroxy-2-oxoglutarate aldolase (HOA), key enzymes for glycine synthesis from hydroxyproline, decreased in the liver and kidneys between postnatal day 0 and day 21, but increased in the pancreas and small intestine over the same period of time (P < 0.05). Similar results were obtained for expression of mRNAs for those enzymes. The enzymatic activities and expression of mRNAs for serine hydroxymethyl transferase (SHMT) and threonine dehydrogenase (TDH) increased between days 0 and 21 of age in most tissues (P < 0.05). Localization of OH-POX and POX shifted from periportal to perivenous hepatocytes in the liver as the animal grew. Tissues incubated with 0 to 5 mM hydroxyproline synthesized glycine in a concentration-dependent manner, but the conversion of glycine into serine was limited. The activities of OH-POX and SHMT were lower in tissues of IUGR piglets (P < 0.05), compared with normal pigs. The activity of TDH did not differ between IUGR and normal piglets. Similar results were obtained for expression of mRNAs of those enzymes. Oral administration of glycine to sow-reared IUGR and normal birth-weight piglets enhanced the concentrations of glycine and serine in plasma, as well as weight gain (P < 0.05), with the dose of 0.4 g glycine/kg BW being the most effective. Consistent with its growth-promoting effect, glycine supplementation augmented the phosphorylation of mechanistic target of rapamycin (MTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and p70S6 kinase (p70S6K) in skeletal muscle, compared with control piglets. The results of this research indicate that: (1) hydroxyproline, an abundant metabolite in sow’s milk and a product of collagen degradation, is a more important substrate for glycine synthesis in tissues of young pigs than serine and threonine; (2) endogenous synthesis of glycine is insufficient for maximal growth of sow-reared IUGR and normal birth-weight piglets; and (3) glycine supplementation enhanced activity of the MTOR signaling pathway in skeletal muscle and growth performance of newborn piglets, especially those with a low birth weight. Collectively, these results indicate an important role for glycine in improving growth of and protein accretion in neonatal pigs.
Hu, Shengdi (2017). Endogenous Synthesis of Glycine from Hydroxyproline in Neonatal Pigs. Doctoral dissertation, Texas A & M University. Available electronically from