Glutamine Metabolism in Very Low Birth Weight Infants

Abstract

To quantitate glutamine kinetics in premature infants and determine whether glutamine affects leucine metabolism. 11 very low birth weight (< 1250 g) neonates received 4-h i.v. infusions of L-[2H3]leucine and L-[13C5]glutamine, along with orogastric infusion of L-[I-13C]leucine and L-[I-13C]glutamine on the 10th d of life and in the fed state. Patients were receiving parenteral nutrition and were randomized to receive either hypocaloric, enteral preterm formula alone (controls; n = 5), or glutamine (0.2 g.kg-1.d-1 on the day of the study) supplemented formula (GL.n; n = 6). The rates of appearance (Ra) of leucine and glutamine, and their rates of splanchnic extraction were determined from isotopic enrichments in plasma at steady state. Leucine release from protein breakdown did not differ between groups (123 +/- 51 versus 162 +/- 94 mumol.kg-1h-1 in the controls and GLN group, respectively). Glutamine de novo synthesis accounted for > 80% of overall glutamine Ra, and was similar in both groups (626 +/- 177 versus 525 +/- 86 mumol.kg-1.h-1; NS); 46 +/- 16% and 53 +/- 31% of the enteral glutamine underwent first-pass splanchnic extraction in the controls and GLN group, respectively. These findings indicate that the pathways of glutamine de novo synthesis and glutamine utilization in the splanchnic bed are functional in very low birth weight humans by the 10th d of life. Glutamine supplementation provided at low doses on a hypocaloric regimen results in no apparent differences in flux of glutamine or leucine.

Acute Effects of Intravenous Glutamine Supplementation on Protein Metabolism in Very Low Birth Weight Infants: A Stable Isotope Study

“…This result is consistent with our earlier studies: in another group of VLBW infants, enteral glutamine delivery was associated with a trend toward a reduction in B Leu ; in that previous study, the approximately 16% decline, however, failed to reach statistical significance (24). Besides a type II statistical error, several differences in study design can, however, account for the difference: in that earlier study, glutamine was supplied via the enteral route, and the dose was only 40% of that used in the current study (0.2 versus 0.5 g · kg Ϫ1 · d Ϫ1 ).…”

“…This is, however, unlikely as 1) proteolysis seems to be somehow insulin resistant in neonates (26), and amino acids may be the main factor regulating proteolysis in the neonatal period; and 2) moreover, although insulin levels were not measured in the present study, we failed to observe any rise in insulin secretion in healthy adults given large oral doses of glutamine in previous studies [(11), and Darmaun et al unpublished personal results]. In earlier studies, we found glutamine utilization rate and metabolic clearance rate (glutamine utilization rate divided by plasma glutamine concentration) to be much higher in VLBW infants than older children (24). The higher clearance rate of plasma glutamine may point to a greater glutamine requirement in VLBW infants.…”

Majority of Dietary Glutamine Is Utilized in First Pass in Preterm Infants

“…Dietary digested amino acids can be used for intestinal energy generation; for conversion via transamination into other amino acids, metabolic substrates, and biosynthetic intermediates; and for tissue growth. Previous studies in neonates showed a considerable intestinal amino acid metabolism, with some amino acids that are extensively catabolized, while others are presumed to be incorporated to a great extend in mucosal cellular or excreted (glyco-)proteins (5)(6)(7)(8)(9).…”

“…In human adults, Matthews et al (15,16) found that the splanchnic extraction of glutamine was 60 to 80% of the dietary intake, of which oxidation was a major metabolic fate. In preterm infants, Darmaun et al (5) showed that glutamine is extensively extracted from the enteral lumen. Whether preterm infants sequester and oxidize the same amount of dietary glutamine has not yet been investigated.…”

Suplementação enteral e parenteral com glutamina em neonatos pré-termo e com baixo peso ao nascer

“…Esses resultados sugerem que a glutamina administrada, via enteral, foi completamente metabolizada pelo intestino e, portanto, não atingiu a circulação sangüínea (Parimi et al, 2004). Não obstante, em outro estudo (Darmaun et al, 1997), apenas cerca de 46% da glutamina administrada junto à nutrição enteral (0,2 g/kg/dia) foram extraídas pelo intestino durante o processo de absorção em neonatos PT e com BPN com 10 dias de vida.…”