Whole-Body Protein Turnover in Preterm Appropriate for Gestational Age and Small for Gestational Age Infants: Comparison of [15N]Glycine and [1-13C]Leucine Administered Simultaneously

Department of Paediatrics, Academic Hospital Rotterdam/Sophia Children's Hospital, Erasmus University Rotterdam, The Netherlands.
Pediatric Research (Impact Factor: 2.31). 05/1995; 37(4 Pt 1):381-8. DOI: 10.1203/00006450-199504000-00001
Source: PubMed
Measurements of whole-body protein turnover in preterm infants have been made using different stable isotope methods. Large variation in results has been found, which could be due to different clinical conditions and/or the use of different tracers. We studied 14 appropriate for gestational age and nine small for gestational age orally fed preterm infants using [15N]glycine and [1-(13)C]leucine simultaneously, which allowed us to make a comparison of commonly used methods to calculate whole-body protein turnover. Whole-body protein turnover was calculated from 15N enrichment in urinary ammonia and urea after [15N]-glycine administration and from the 13C enrichment in expired CO2 after administration of [1-(13)C]leucine. Enrichment of alpha-ketoisocaproic acid after [1-(13)C]leucine constant infusion was measured as a direct parameter of whole-body protein turnover. Group means for whole-body protein turnover using [15N]glycine or [1-(13)C]leucine ranged from 10 to 14 g.kg-1.d-1, except when using the end product method that assumes a correlation between leucine oxidation and total nitrogen excretion. We found very low 15N enrichment of urinary urea in the majority of small for gestational age infants. These infants also had a lower nitrogen excretion in urine and oxidized less leucine. Nitrogen balance was higher in small for gestational age infants (416 +/- 25 mg.kg-1.d-1) compared with appropriate for gestational age infants (374 +/- 41 mg.kg-1.d-1, p = 0.003). [15N]Glycine does not seem to exchange its label with the body nitrogen pool to a significant degree and is therefore not always suitable as a carrier for 15N in protein turnover studies in premature infants.


Available from: Johannes B van Goudoever, Mar 10, 2016
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    • "† Calculated as a percent of mean concentration at 2 h [ either route of feeding still had not achieved steady state during the latter half of a 12-h fast. The observed increase in BCAA concentrations is of particular importance because leucine is commonly used as a tracer to quantify protein metabolism in neonates (19, 20). Estimates of endogenous protein breakdown have been reported from tracer studies using leucine, phenylalanine, or both amino acids. "
    [Show abstract] [Hide abstract] ABSTRACT: Kinetics studies in neonates are important to establish the requirement for amino acids and to understand the mechanisms of normal and altered metabolism. During kinetics experiments, plasma amino acid concentrations should be in steady state. Our objective was to determine whether 12 h of fasting, after parenteral or enteral feeding, resulted in a steady state in concentrations of amino acids. Two-day-old piglets were implanted with catheters (d 0), and randomly assigned to either intragastric (i.g., n = 6) or i.v. (n = 6) feeding. On d 5, piglets were fasted for 12 h. During the first 2 h, plasma concentrations of almost all amino acids declined except asparagine (i.g. and i.v.), tyrosine (i.v.), and glycine (i.v.), which increased. Only i.g. glycine did not change. Between 2 and 12 h, the only indispensable amino acids that did not change were phenylalanine (i.v.) and histidine (i.g. and i.v.). The branched-chain amino acids increased during this period (i.v. and i.g.). The greatest change was tyrosine, increasing 13% (i.v.) and 32% (i.g.) per hour. After 12 h of refeeding, glycine, serine, threonine, and asparagine concentrations were lower than baseline (p<0.05) in the i.v. group. In i.g. fed piglets, only threonine remained below baseline (p<0.05), and arginine was greater than baseline (p<0.05). Differences between i.v. and i.g. may be the result of impaired small intestinal metabolism secondary to parenteral feeding. In neonatal pigs, most plasma amino acids were unstable during 12 h of fasting. Thus, kinetics studies that require a steady state must be conducted in the fed state.
    Full-text · Article · Dec 2000 · Pediatric Research
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    • "Unfortunately, at this stage the mechanism that mediates these apparently specific effects of colostrum is not known, although it appears that neither insulin nor insulin-like growth factor 1 are involved directly. Indeed, given the response in the central nervous system, it is tempting to speculate that the colostrum stimulation of protein synthesis is not a response to a soluble growth factor or hormone absorbed by the neonate, but that et al. (1991, 1992, 1994, 1995); Kandil et al. (1991); Beaufrere et al. (1992); van Goudoever et al. (1995). || The 18-month-old children had recovered from malnutriton and were studied with [ 15 N] glycine. "
    [Show abstract] [Hide abstract] ABSTRACT: The period of growth and development between birth and weaning is crucial for the long-term well-being of the organism. Protein deposition is very rapid, is achieved with a high nutritional efficiency, and is accompanied by marked differences in the growth rates of individual tissues and a series of maturational processes. These important aspects of development occur while the neonate is consuming a single and highly-specific food source, milk. Surprisingly, although there is a clear relationship between the nutrient density of milk and the growth rate of its recipient, this relationship does not apply to the overall amino acid composition of mixed milk proteins. Some amino acids, notably glycine and arginine, are supplied in milk in quantities that are much less than the needs of the neonate. The milk-fed neonate is therefore capable of carrying out a tightly-regulated transfer of N from amino acids in excess to those that are deficient. The rapid growth of the neonate is supported by a high rate of tissue protein synthesis. This process appears to be activated by the consumption of the first meals of colostrum. Recent research has identified that skeletal muscle and the brain are specifically responsive to an unidentified factor in colostrum. Following the initial anabolic response the rate of protein synthesis in some tissues, notably muscle, falls from birth to weaning. This decrease reflects a progressively smaller anabolic response to nutrient intake, which not only involves an overall fall in the capacity for protein synthesis, but also in responses to insulin and amino acids. The study of growth and protein metabolism, and their regulation in the neonate is not only important for pediatrics, but may provide important pointers to more general aspects of regulation that could be applied to the nutrition of the mature animal.
    Full-text · Article · Mar 2000 · Proceedings of The Nutrition Society
  • [Show abstract] [Hide abstract] ABSTRACT: Changes in parenteral nutrition of the term and preterm newborns There is an increase in survival rates of very low birth weight infants in recent years. The rise in survival of very low birth weight infants is associated with increased use of parenteral nutrition and change of practice in parenteral nutrition, since very low birth weight infants can not be fed ente- rally in early period of life. Until recently, it was also common practice to initiate an aminoacid in- fusion at 0.5 g/kg/day between 24 and 48 hours of life and then to initiate a lipid emulsion at 0.5 g/kg/day 24 hours later. Both infusions would then be increased by 0.5 g/kg/day increments to 3- 3.5 g/kg/day. Reports that an aminoacid infusion providing at least 1.5 g/kg/day of protein is requ- ired to achieve a positive protein balance, have resulted in recommendations that at least 1.5 g/kg/day of protein should be started within the first 24 hours after birth and then increased to 3.5- 4 g/kg/day by 0.5-1 g/kg/day increments. Early aggressive nutrition is a new concept which means initiation of an aminoacid infusion providing about 3 g/kg/day within hours of birth, initiation of a lipid emulsion of 0.5-1 g lipid/kg/day within 24-30 hours of birth, with subsequent increases pro- viding up to 3.5-4 g protein/kg/day and 2-3 g lipid/kg/day for the following days. A daily energy in- take should be 120-130 kcal/kg/day in healthy preterm neonates and 100-120 kcal/kg/day in he- althy term neonates. Aim of this strategy is to provide nutrient intakes that permit the rate of post- natal growth and the composition of weight gain to approximate that of a normal fetus of the sa- me postmentruel age.
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