Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.
Exp Biol Med (Maywood). 2023 Sep;248(17):1446-1458. doi: 10.1177/15353702231199080. Epub 2023 Oct 14.
This study tested the hypothesis that the synthesis of glycine from 4-hydroxyproline (an abundant amino acid in milk and neonatal blood) was impaired in tissues of piglets with intrauterine growth restriction (IUGR), thereby contributing to a severe glycine deficiency in these compromised neonates. At 0, 7, 14, and 21 days of age, IUGR piglets were euthanized, and tissues (liver, small intestine, kidney, pancreas, stomach, skeletal muscle, and heart) were obtained for metabolic studies, as well as the determination of enzymatic activities, cell-specific localization, and expression of mRNAs for glycine-synthetic enzymes. The results indicated relatively low enzymatic activities for 4-hydroxyproline oxidase (OH-POX), proline oxidase, serine hydroxymethyltransferase, threonine dehydrogenase (TDH), alanine: glyoxylate transaminase, and 4-hydroxy-2-oxoglutarate aldolase in the kidneys and liver from 0- to 21-day-old IUGR pigs, in the pancreas of 7- to 21-day-old IUGR pigs, and in the small intestine and skeletal muscle (except TDH) of 21-day-old IUGR pigs. Accordingly, the rates of conversion of 4-hydroxyproline into glycine were relatively low in tissues of IUGR piglets. The expression of mRNAs for glycine-synthetic enzymes followed the patterns of enzymatic activities and was also low. Immunohistochemical analyses revealed the relatively low abundance of OH-POX protein in the liver, kidney, and small intestine of IUGR piglets, and the lack of OH-POX zonation in their livers. These novel results provide a metabolic basis to explain why the endogenous synthesis of glycine is insufficient for optimum growth of IUGR piglets and have important implications for improving the nutrition and health of other mammalian neonates including humans with IUGR.
本研究检验了这样一个假设，即在宫内生长受限（IUGR）的仔猪组织中，4-羟脯氨酸（牛奶和新生儿血液中的一种丰富氨基酸）合成甘氨酸的能力受损，从而导致这些受损新生儿严重缺乏甘氨酸。在 0、7、14 和 21 天龄时，处死 IUGR 仔猪，并进行代谢研究，获取组织（肝脏、小肠、肾脏、胰腺、胃、骨骼肌和心脏），以确定酶活性、细胞特异性定位以及甘氨酸合成酶的 mRNA 表达。结果表明，0-21 日龄 IUGR 仔猪的肾脏和肝脏、7-21 日龄 IUGR 仔猪的胰腺以及 21 日龄 IUGR 仔猪的小肠和骨骼肌（除 TDH 外）中，4-羟脯氨酸氧化酶（OH-POX）、脯氨酸氧化酶、丝氨酸羟甲基转移酶、苏氨酸脱氢酶（TDH）、丙氨酸：乙醛酸转氨酶和 4-羟基-2-氧代戊二酸醛缩酶的酶活性相对较低。相应地，4-羟脯氨酸转化为甘氨酸的速率在 IUGR 仔猪的组织中相对较低。甘氨酸合成酶的 mRNA 表达遵循酶活性的模式，也较低。免疫组织化学分析显示，IUGR 仔猪的肝脏、肾脏和小肠中 OH-POX 蛋白的含量相对较低，其肝脏中缺乏 OH-POX 分区。这些新的结果为解释为什么内源性甘氨酸合成不足以满足 IUGR 仔猪的最佳生长提供了代谢基础，并对改善包括人类 IUGR 在内的其他哺乳动物新生儿的营养和健康具有重要意义。
