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Glutamine and leucine nitrogen kinetics and their relation to urea nitrogen in newborn infants
Prabhu S Parimi1, Srisatish Devapatla, Lourdes Gruca
1Department of Pediatrics, Robert Schwartz M.D. Center for Metabolism and Nutrition, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109-1998, USA.
Insights
Newborn infants exhibit high glutamine turnover, crucial for protein synthesis and energy metabolism. This study reveals its link to leucine metabolism and urea synthesis, highlighting its role in infant development.
Area of Science:
- Biochemistry
- Neonatal Physiology
- Nutritional Metabolism
Background:
- Infant metabolism differs significantly from adults.
- Understanding nutrient kinetics is vital for neonatal health.
Purpose of the Study:
- Quantify glutamine kinetics in newborns.
- Relate glutamine metabolism to leucine transamination and urea synthesis.
- Investigate metabolic responses to feeding in different infant groups.
Main Methods:
- Utilized stable isotope tracers ([5-(15)N]glutamine, [1-(13)C,(15)N]leucine, [(2)H(5)]phenylalanine, [(15)N(2)]urea).
- Measured kinetics during fasting and post-formula feeding.
- Analyzed data from appropriate-for-gestational-age, small-for-gestational-age, and infants of diabetic mothers.
Main Results:
- Newborns showed higher leucine nitrogen and glutamine kinetics than adults during fasting.
- De novo synthesis comprised ~85% of glutamine turnover.
- Formula feeding increased leucine turnover but decreased glutamine and urea appearance rates.
- Leucine nitrogen turnover correlated positively with glutamine turnover.
- Glutamine flux inversely correlated with urea synthesis rate.
Conclusions:
- Newborn glutamine turnover is linked to high anaplerotic flux supporting protein turnover.
- Glutamine serves as a key nitrogen source for synthesis and protein accretion in neonates.
- Metabolic pathways are distinct in newborns compared to adults, influenced by feeding status.
Abstract:
Glutamine kinetics and its relation to transamination of leucine and urea synthesis were quantified in 16 appropriate-for-gestational-age infants, four small-for-gestational-age infants, and seven infants of diabetic mothers. Kinetics were measured between 4 and 5 h after the last feed (fasting) and in response to formula feeding using [5-(15)N]glutamine, [1-(13)C,(15)N]leucine, [(2)H(5)]phenylalanine, and [(15)N(2)]urea tracers. Leucine nitrogen and glutamine kinetics during fasting were significantly higher than those reported in adults. De novo synthesis accounted for approximately 85% of glutamine turnover. In response to formula feeding, a significant increase (P = 0.04) in leucine nitrogen turnover was observed, whereas a significant decrease (P = 0.002) in glutamine and urea rate of appearance was seen. The rate of appearance of leucine nitrogen was positively correlated (r(2) = 0.59, P = 0.001) with glutamine turnover. Glutamine flux was negatively correlated (r(2) = 0.39, P = 0.02) with the rate of urea synthesis. These data suggest that, in the human newborn, glutamine turnover is related to a high anaplerotic flux into the tricarboxylic acid cycle as a consequence of a high rate of protein turnover. The negative relationship between glutamine turnover and the irreversible oxidation of protein (urea synthesis) suggests an important role of glutamine as a nitrogen source for other synthetic processes and accretion of body proteins.