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

Abstract

Glutamine is a conditionally essential amino acid for very low-birth weight infants by virtue of its ability to play an important role in several key metabolic processes of immune cells and enterocytes. Although glutamine is known to be used to a great extend, the exact splanchnic metabolism in enterally fed preterm infants is unknown. We hypothesized that preterm infants show a high splanchnic first-pass glutamine metabolism and the primary metabolic fate of glutamine is oxidation. Five preterm infants (mean Ϯ SD birth weight 1.07 Ϯ 0.22 kg and GA 29 Ϯ 2 wk) were studied by dual tracer ([U-13 C]glutamine and [ 15 N 2 ]glutamine) crossover techniques on two study days (at postnatal week 3 Ϯ 1 wk). Splanchnic and whole-body glutamine kinetics were assessed by plasma isotopic enrichment of [U- CO 2 enrichments. Mean fractional first-pass glutamine uptake was 73 Ϯ 6% and 57 Ϯ 17% on the study days. The splanchnic tissues contributed for a large part (57 Ϯ 6%) to the total amount of labeled carbon from glutamine retrieved in expiratory air. Dietary glutamine is used to a great extent by the splanchnic tissues in preterm infants and its carbon skeleton has an important role as fuel source. A fter birth, very low-birth weight infants (VLBW) infants are exposed to stress-induced protein wasting and intestinal infirmity. Given the key role of the intestine in the conservation of neonatal wellness, there has been substantial interest in the magnitude of first-pass splanchnic metabolism of dietary amino acids (1-4). 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 (5-9).Glutamine, a conditionally essential amino acid for VLBW infants, might play a versatile role in both maintenance of gut trophicity and in nitrogen homeostasis by interorgan shuttling of carbon and nitrogen. Glutamine plays a central role as a substrate for a number of aminotransferases that are responsible for the synthesis of asparagine, glucosamine, NAD, purines, and pyrimidines (10). In animal studies, the small intestine is a major organ for glutamine utilization (11,12). Moreover, in in vitro experiments, glutamine has been shown to be the most important oxidative fuel source for rapidly dividing cells such as cells from gut and the immune system (13,14). 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 ...

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