Abstract
The intestine is a major site of amino acid metabolism, especially in neonates. The energy needed for the metabolic processes in neonatal animals is derived from dietary glucose and amino acids. No data are available showing that dietary amino acids function as intestinal fuel source in human neonates as well. We hypothesized that preterm infants show a high splanchnic first-pass glutamate metabolism and the primary metabolic fate of glutamate is oxidation. Five preterm infants (birth weight 1.2 ± 0.2 kg, gestational age 29 ± 1 wk) were studied by dual tracer ([U-13C]glutamate and [D3]glutamate) techniques on two study days (within postnatal d 14–19). Splanchnic and whole-body glutamate kinetics were assessed by plasma isotopic enrichment of [U-13C]glutamate and [D3]glutamate and breath 13CO2 enrichment. Fractional first-pass glutamate uptake was 77 ± 18% on d 1, and 70 ± 7% on d 2, mean 74 ± 13%. Almost all (86 ± 7%) of the glutamate used in the first pass is directed toward oxidation. There is a high splanchnic fractional first-pass uptake and a high oxidation rate of glutamate in preterm infants. Glutamate is an important source of energy for the splanchnic tissues in preterm infants receiving full enteral feeding.
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Abbreviations
- APE:
-
atom percent excess
- GSH:
-
glutathione
- ORS:
-
oral rehydration solution
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The authors thank Ko Hagoort for critical review of the manuscript.
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Sophia Foundation for Medical Research (grant 417), The Netherlands, Numico Foundation, Wageningen, The Netherlands, and Ajinimoto, Japan.
Appendix 1
Appendix 1
Glutamate flux during i.v. infusion was calculated as follows (7):
MATH
where QIV is the flux of the i.v. infused tracer [μmol/(kg · h)], iglu_iv is the i.v. glutamate infusion rate [μmol/(kg · h)], and IEi and IEp are the isotopic enrichments (mol% excess) of i.v. administered [U-13C or D3]glutamate in the infusate or in plasma at steady state, respectively.
The flux for the intragastrically administered tracer was calculated as follows:
MATH
where QIG is the flux of the intragastrically infused tracer [μmol/(kg · h)], iglu_ig is the intragastric glutamate infusion rate (μmol/(kg · h), and IEi, and IEp are the isotopic enrichments (mol% excess) of intragastrically administered [U-13C or D3]glutamate in the infusate or in plasma at steady state, respectively.
First-pass glutamate uptake was calculated as:
MATH
where U is the first-pass glutamate uptake μmol/(kg · h)], QIG is the flux of the intragastrically administered glutamate tracer [μmol/(kg · h)], QIV is the flux of the i.v. administered glutamate tracer [μmol/(kg · h)], and I is the intake of enteral glutamate [μmol/(kg · h)].
Whole-body CO2 production was estimated as:
MATH
where iB is the infusion rate of [13C]sodium bicarbonate [(μmol/(kg · h)], IEiB is the enrichment (mol% excess) of [13C]bicarbonate in the bicarbonate infusate, and IEB is the 13CO2 enrichment at steady state during the labeled bicarbonate infusion (mol% excess). Splanchnic and whole-body glutamate oxidation rates were determined under the assumption that CO2 production during [13C]bicarbonate infusion equals the labeled glutamate tracer infusion. Assuming a constant CO2 production rate during the 7 h of infusion, it is not necessary to use a correction factor for retention of [13C]bicarbonate in the body (25).
Glutamate oxidation was calculated by multiplying recovery of [13C]glutamate in expiratory air with the rate of appearance of glutamate (7,25). The fraction of glutamate oxidized using the enrichment of the i.v. [U-13C]glutamate infusion on study d 1 and intragastric [U-13C]glutamate on study d 2 was calculated as:
MATH
where IEglu and IEB are 13CO2 enrichments (mol% excess) in expired breath at steady state during i.v. (d 1) or intragastric (d 2) [U-13C]glutamate and [13C]bicarbonate infusion. The iglu is multiplied by a factor of 5 to account for the number of labeled C atoms.
Whole-body glutamate oxidation (day 1) was calculated as:
MATH
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Riedijk, M., de Gast-Bakker, DA., Wattimena, J. et al. Splanchnic Oxidation Is the Major Metabolic Fate of Dietary Glutamate in Enterally Fed Preterm Infants. Pediatr Res 62, 468–473 (2007). https://doi.org/10.1203/PDR.0b013e31813cbeba
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DOI: https://doi.org/10.1203/PDR.0b013e31813cbeba
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