Threonine kinetics in preterm infants fed their mothers' milk or formula with various ratios of whey to casein

Darling, Pauline B.; Dunn, Michael; Sarwar, Ghulam; Brookes, Steve; Ball, Ronald O.; Pencharz, Paul B.

doi:10.1093/ajcn/69.1.105

Cited by 52 publications

(67 citation statements)

References 43 publications

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“…One possibility is that threonine is being converted to glycine. In humans, the TDH pathway accounts for only 7-11% of threonine oxidation [16] in adults whereas up to 44% of oxidation is through this pathway in preterm infants [24]. Glycine is also important during gestation in rodents [25] and even a small increase in the conversion of threonine to glycine may lead to a considerable increase in the demand because of the high glycine flux.…”

Section: Discussionmentioning

confidence: 99%

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

Rees¹,

Hay²,

Antipatis³

2006

Reprod. Nutr. Dev.

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-To characterise the effects of dietary protein content on threonine metabolism during pregnancy, rats were fed diets containing 18% or 9% protein and then killed at different stages of gestation. Serum threonine concentrations fell significantly faster in the animals fed the diet containing 9% protein when compared to those fed the diet containing 18% protein. On day 4 of gestation the rate of threonine oxidation was higher in maternal liver homogenates prepared from the animals fed the diet containing 18% protein. The rate of threonine oxidation by liver homogenates fell as gestation proceeded in both diet groups. The activity of threonine dehydrogenase in the maternal liver was unaffected by dietary protein content at all stages of gestation. Serine-threonine dehydratase activity in homogenates of the maternal liver was transiently increased during the early stages of gestation in the animals fed high protein diets but was unchanged in the low protein groups. There was an increase in serine-threonine dehydratase activity in the kidney during the later stages of gestation but this was unaffected by the protein content of the maternal diet. These data show that the changes in free threonine concentrations cannot be accounted for through changes in the oxidation rate and suggest that some other factor influences the unusual metabolism of this amino acid during gestation. threonine dehydratase / threonine dehydrogenase / protein metabolism / pregnancy / foetus / metabolic programming Abbreviations: SDH, serine/threonine dehydratase; TDH, threonine dehydrogenase; PCA, perchloric acid; TCA, trichloroacetic acid.

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Section: Discussionmentioning

confidence: 99%

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

Rees¹,

Hay²,

Antipatis³

2006

Reprod. Nutr. Dev.

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“…Cofactors include pyridoxal (vitamin B6, or nicotinamide adenine dinucleontide) and co-enzyme A. * Denotes the fate of the labelled carbon of L-(1-13 C)threonine through the degradative pathways (Bird and Nunn, 1983;Darling et al, 1999).…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

Scientific opinion on the safety and efficacy of L‐threonine produced by Escherichia coli (FERM BP‐10942) for all animal species based on a dossier submitted by Ajinomoto Eurolysine SAS

Feed¹

2013

EFS2

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The product L-threonine, technically pure, is an essential amino acid that contains by specification ≥ 98 % Lthreonine. It is produced by a genetically modified Escherichia coli strain. Neither the production strain nor its recombinant DNA was detectable in the final product. The final product does not raise safety concerns with regard to the genetic modification. L-Threonine, technically pure, is considered safe for the target animals when used to meet the requirements. The toxicological studies, including mutagenicity tests, performed with the additive or other sources of L-threonine did not reveal any toxic effect. Since the composition of tissues and products of animal origin will not be changed by the use of L-threonine in animal nutrition, and considering the high purity of the product under assessment, no risks are expected for the consumer from the use of L-threonine, technically pure, as a feed additive. The product is not irritating to the skin or eyes and is not likely to be a skin sensitiser. Although there is a potential for user exposure by inhalation, there is no evidence of acute toxicity by the inhalation route. The use of the product as a feed additive does not represent a risk to the environment. LThreonine, technically pure, is considered as an efficacious source of L-threonine for all animal species. Response in ruminants requires some degree of protection of threonine from ruminal degradation. SUMMARYFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of the product L-threonine, technically pure, for all animal species.Threonine is an essential amino acid, considered as the second limiting amino acid in pig feed and probably as the third limiting in poultry feed. Supplementing feedingstuffs with free threonine would ensure that the animal requirements for that amino acid are met.The product L-threonine, technically pure, contains by specification ≥ 98 % L-threonine. It is produced by a genetically modified Escherichia coli strain.Neither the production strain nor its recombinant DNA was detectable in the final product. The final product does not raise safety concerns with regard to the genetic modification.L-Threonine, technically pure, is considered safe for the target animals when used to meet the requirements.The toxicological studies, including mutagenicity tests, performed with the additive or other sources of L-threonine did not reveal any toxic effect. Since the composition of tissues and products of animal origin will not be changed by the use of L-threonine in animal nutrition, and considering the high purity of the product under assessment, no risks are expected for the consumer from the use of Lthreonine, technically pure, as a feed additive.The product is not irritating to the skin or eyes and is not likely to be a skin sensitiser. Although there is a potential for user exposure by inhalation, there is no evidence of acute tox...

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“…Earlier we published a study in which we showed that formula-fed preterm infants did not increase threonine degradation in response to increased threonine intake (8). Conversely infants fed their mother's own milk increased their oxidation of threonine and thereby could handle the relatively high load of threonine present in human milk protein (8). Since casein-dominant formulas are known to cause elevations in plasma phenylalanine and tyrosine levels (6,9,10) we decided to also investigate the ability of preterm neonates to handle an increased load of phenylalanine and tyrosine and compare the results with infants fed their mother's own milk.…”

mentioning

confidence: 98%

“…The initial approach was to produce infant formulas based on a whey:casein ratio of 60:40, approximating that in human milk, but this resulted in infants with high plasma threonine levels (6). Earlier we published a study in which we showed that formula-fed preterm infants did not increase threonine degradation in response to increased threonine intake (8). Conversely infants fed their mother's own milk increased their oxidation of threonine and thereby could handle the relatively high load of threonine present in human milk protein (8).…”

mentioning

confidence: 98%

“…Since casein-dominant formulas are known to cause elevations in plasma phenylalanine and tyrosine levels (6,9,10) we decided to also investigate the ability of preterm neonates to handle an increased load of phenylalanine and tyrosine and compare the results with infants fed their mother's own milk. To serve as a basis for comparison we studied preterm infants fed formulas that were made to be identical except for their whey:casein ratio; the ratios used were 60:40, 40:60, and 20:80 (8). Earlier work showed that the whey to casein ratio does not affect protein accretion (11).…”

mentioning

confidence: 99%

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Phenylalanine Kinetics Differ between Formula-Fed and Human Milk–Fed Preterm Infants

Darling¹,

Dunn²,

Gilani³

et al. 2004

The Journal of Nutrition

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Infants fed casein-dominant formulas have higher plasma phenylalanine and tyrosine concentrations than those fed mother's milk. Conversely, elevated plasma threonine concentrations are observed in infants fed whey-dominant formulas. We recently showed that formula-fed preterm infants have a lower capacity to degrade threonine than do preterm infants fed mother's milk. We hypothesized that these same infants (n ϭ 18) would differ in their catabolism of phenylalanine in response to phenylalanine loads provided by formulas with increasing casein content of formulas (whey:casein 60:40, 40:60, and 20:80) compared with preterm infants fed mother's milk. Plasma phenylalanine concentrations significantly rose (49, 46, 79 mol ⅐ L Ϫ1 for whey:casein 60:40, 40:60, and 20:80, respectively, pooled SD 8, P Ͻ 0.05); and plasma phenylalanine concentrations in infants fed mother's milk were low (40 Ϯ 4 mol ⅐ L Ϫ1 ). Using [1-13 C]phenylalanine tracer and 13 CO 2 production in breath we found that although there was a significant positive relation between phenylalanine oxidation and phenylalanine intake in formula-fed infants (r 2 ϭ 0.43, P ϭ 0.03), these infants were not able to increase their oxidation of phenylalanine enough to prevent a significant rise in plasma phenylalanine when fed the 20:80 formula. Compared to infants fed mother's milk, formula-fed infants had significantly lower phenylalanine oxidation (39.1 vs. 30.7% of phenylalanine intake, respectively, P Ͻ 0.05). We conclude that one of the mechanisms for the differences in plasma amino acid concentration between formula-fed and mother's milk-fed preterm infants may be in vivo down-regulated catabolism of 2 important essential amino acids (phenylalanine in addition to threonine) in formula-fed preterm infants.

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Threonine kinetics in preterm infants fed their mothers' milk or formula with various ratios of whey to casein

Cited by 52 publications

References 43 publications

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

Scientific opinion on the safety and efficacy of L‐threonine produced by Escherichia coli (FERM BP‐10942) for all animal species based on a dossier submitted by Ajinomoto Eurolysine SAS

Phenylalanine Kinetics Differ between Formula-Fed and Human Milk–Fed Preterm Infants

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