Decreased cysteine and proline synthesis in parenterally fed, premature infants

Abstract

Little is known about the amino acid (AA) biosynthetic capacity and requirements of premature infants. This study assessed the synthesis of seven biochemically nonessential AA from a universal precursor, glucose, in stable, parenterally fed, premature neonates. Seven infants (six boys, one girl) were studied at a mean age of 6.3 ± 0.6 (SEM) days; mean gestational age was 29.7 ± 1.3 (SEM) weeks, and mean birth weight was 1,222.8 ± 176.5 (SEM) grams. All infants were parenterally fed a mixture of 7.5% to 12.5% dextrose and 2.2% Trophamine, with or without lipid. Mean caloric intake was 93 ± 8.4 (SEM) kcal/kg/d, and total AA intake was standardized at 2.86 g/kg/d AA, plus supplemental cysteine (30 mg/g AA/d). Each infant received a 4-hour continuous, unprimed intravenous infusion of a stable isotope tracer of D-[U 13C] glucose (200 mg/kg). Blood samples were obtained before and at the end of the infusion. Conversion of the glucose tracer into seven biochemically nonessential AA (cysteine [Cys], proline [Pro], aspartate [Asp], serine [Ser], glutamate [Glu], alanine [Ala], and glycine [Gly]) was assessed by measuring their isotopic enrichment in plasma, using gas chromatography/mass spectrometry ( GC MS ), and expressed as mole percent excess (MPE) (mean ± SEM). The isotopic enrichment of plasma glucose was also measured using GC MS . Free plasma AA concentrations (mean ± SD) were measured using an automated amino acid analyzer. Mean MPE for M + 1, M + 2 and M + 3 Cys, and for M + 1 and M + 3 Pro were not significantly different from 0; M + 2 Pro barely achieved statistical significance ( P = .048). In contrast, there was significant ( P < .05) enrichment of all isotopomers of all the other test AA except M + 2 Ala ( P = .06). The mean free plasma Cys concentration (29.2 ± 13.4 μmol/L) was five-fold lower than the published value for term infants (153 ± 25.5 μmol/L), despite supplementation. Detectable enrichment of all glucose isotopomers confirmed precursor incorporation into the glycolytic/gluconeogenic pathways; the M + 6 isotopomer (precursor) enrichment was 6.87 ± 0.53 MPE. These results provide in vivo evidence to suggest that Cys and Pro are essential amino acids in parenterally fed, premature neonates.