090 The hydroxyproline–glycine pathway for gl.ycine synthesis in neonatal pigs

Hu, Shengdi; Nawaratna, Gayan; Long, B. D.; Bazer, Fuller W.; Johnson, Greg A.; Brosnan, John T.

doi:10.2527/asasann.2017.090

Cited by 6 publications

(3 citation statements)

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“…Furthermore, in contrast to NBW piglets, there was no synthesis of glycine from 4-hydroxyproline in the skeletal muscle of 0-to 14-day-old IUGR piglets, and the rate of conversion of 5 mM 4-hydroxyproline into glycine in the muscle of 21-day-old IUGR piglets was only 17% of that for NBW piglets. Taken together, our results explain why glycine is severely deficient in IUGR piglets, 35 and why glycine is likely a major limiting factor for their optimal growth and development. 7 Besides the OH-POX-glycine pathway, the SHMT-glycine pathway was also impaired in tissues of IUGR piglets as indicated by the much lower activity of SHMT (Table 1) when compared with age-matched NBW littermates.…”

Section: Discussionsupporting

confidence: 54%

“…13,34 We have recently reported that concentrations of glycine in the plasma of 0-to 21-day-old IUGR piglets (~0.5-0.6 mM) is only 50% of that for age-matched NBW piglets; thus, this severe deficiency of glycine limits the growth of IUGR piglets. 35 At present, little is known about the mechanisms responsible for glycine deficiency in young mammals (including piglets) with IUGR. To address this issue, we examined key enzymes in the metabolic pathways for de novo synthesis of glycine in IUGR piglets (Table 1).…”

Section: Discussionmentioning

confidence: 99%

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Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs with intrauterine growth restriction

Hu,

He,

Bazer

et al. 2023

Exp Biol Med (Maywood)

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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.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs with intrauterine growth restriction

Hu,

He,

Bazer

et al. 2023

Exp Biol Med (Maywood)

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“…Adult humans consume 0.75 g protein/kg BW/ day b Yu et al (1985). This value refers to the healthy adult consuming 1.5 g protein/day c Meléndez-Hevia et al (2009) d The value is estimated from the plasma flux of glycine (22.6 g/day in the 70-kg healthy adult; Ginson et al 2002) and the net conversion of plasma glycine into serine (i.e., 6% of plasma glycine flux; Butterworth et al 1958) e Starck et al (2018) f The average value of 10.1 g/day for the healthy adult consuming 0.75 g protein/day (Gibson et al 2002) and 8.09 g/day for the healthy adult consuming 1.5 g protein/day (Yu et al 1985) g The value was calculated on the basis of the following: (1) the rate of degradation of mature collagens in the extracellular matrix is equal to the rate of net synthesis of collagen (i.e., the rate of collagen secreted from fibroblasts to the extracellular matrix; 96.5 g/day) in the healthy adult human (Meléndez-Hevia et al 2009); (2) the content of 4-hydroxyproline in collagen is 10.73 g/100 g collagen; Wu et al 2011); and (3) 90% of collagen-derived 4-hydroxyproline is catabolized to form glycine in the healthy adult human (Knight et al 2006);namely, 96.5 × 10.73/100 × 0.90 × 75.07/131.13 = 5.34 extra-intestinal tissues (e.g., liver, skeletal muscle, and skin) also synthesize glycine from 4-hydroxyproline (Hu et al 2017). The half-lives of free hydroxyproline (45 to 80 min) and its di-and tri-peptides (25-100 min) in blood are relatively short and vary with the species and age of mammals.…”

Section: Metabolism Of 4-hydroxyproline In Humansmentioning

confidence: 99%

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

2020

Amino Acids

354

192

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Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-l-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-l-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and antiinflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.

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Amino Acid Metabolism in the Kidneys: Nutritional and Physiological Significance

Zheng²,

2020

Advances in Experimental Medicine and Biology

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090 The hydroxyproline–glycine pathway for gl.ycine synthesis in neonatal pigs

Cited by 6 publications

References 0 publications

Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs with intrauterine growth restriction

Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs with intrauterine growth restriction

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

Amino Acid Metabolism in the Kidneys: Nutritional and Physiological Significance

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