|Shew, Stephen - UNIV OF CAL, LOS ANGELES|
|Keshen, Tamir - WASHINGTON UNIV SCH MED|
|Jaksic, Tom - HARVARD SCHOOL OF MED|
Submitted to: Journal of Pediatric Surgery
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 1, 2005
Publication Date: January 1, 2005
Citation: Shew, S.B., Keshen, T.H., Jahoor, F., Jaksic, T. 2004. Assessment of cysteine synthesis in very low-birth weight neonates using a [13C6]glucose tracer. Journal of Pediatric Surgery. 40:52-56. Interpretive Summary: Cysteine is an amino acid necessary for the synthesis of all proteins, and two very important compounds, the antioxidant glutathione which is necessary to protect the health of cells, and taurine which is important for regulation of nerve function. An adequate supply of cysteine is therefore critical for normal health. Cysteine is obtained from dietary protein and from synthesis in the liver from another amino acid, methionine. It is widely believed that very-low-birth weight (VLBW) premature babies cannot synthesize cysteine because the enzymatic system for cysteine synthesis in the liver is not fully developed. To find out whether this is indeed the case, we measured cysteine synthesis in 12 VLBW premature babies by infusing labeled glucose in which all the carbon atoms were the stable isotope 13C. When glucose is metabolized its carbons are used to make some amino acids so there is transfer of the 13C to the newly formed amino acids. We then analyzed the cysteine in a plasma protein, VLDL-apo B-100, for 13C. This protein is synthesized in the liver and released into the blood. It can therefore only contain 13C labeled cysteine if cysteine is being freshly synthesized in the livers of these VLBW premature babies. We found that there was a significant increase in 13C labeled cysteine derived from VLDL-apo B-100 after infusion of the 13C labeled glucose. Our results show that VLBW babies are capable of cysteine synthesis as evidenced by incorporation of 13C label into VLDL-apo B-100 cysteine, which has important implications for developing therapies for diseases common among VLBW babies.
Technical Abstract: Cysteine is an amino acid necessary for the synthesis of all proteins, the antioxidant glutathione, and the neuromodulator taurine. Whether cysteine is an essential amino acid for premature neonates remains controversial. Using a [13C6]glucose precursor in very-low-birth weight (VLBW) premature neonates, we measured the 13C content of cysteine in hepatically derived apolipoprotein (apo) B-100 and in the plasma to determine whether cysteine synthesis occurs and to relate minimum synthetic capacity to neonatal maturity. Twelve VLBW premature neonates (birth weight, 907 +/- 274 [SD] g; gestational age, 26.8 +/- 2.4 weeks) were studied on day of life 7.8 +/- 4.2 while on total parenteral nutrition (TPN) for 5.6 +/- 4.5 days. A 4-hour intravenous infusion of [13C6]glucose was administered. Blood samples were obtained immediately before and at the end of the infusion. Isotopic enrichment of cysteine was determined by gas chromatography/mass spectrometry. Analysis of variance, Student's t test, and linear regression were used for comparisons. The 13C isotope ratio of apo B-100-derived cysteine after the [13C6]glucose infusion was significantly higher than baseline (18.57 +/- 0.38 [SEM] vs 17.54 +/- 0.25 mol%, P < .05). The 13C isotope ratio of plasma cysteine was also significantly higher than baseline (17.36 +/- 0.25 vs 16.91 +/- 0.16 mol%, P < .05). When expressed as a product/precursor ratio, the mole percent above baseline of [13C]apo B-100 cysteine/[13C6]glucose correlated with birth weight (r = 0.74, P < .01). Very low-birth weight neonates are capable of cysteine synthesis as evidenced by incorporation of 13C label into hepatically derived apo B-100 cysteine and plasma cysteine from a glucose precursor. The minimum capacity for intrahepatic cysteine synthesis appears to be directly proportional to the maturity of the neonate and may impact the capabilities of VLBW neonates to counteract oxidative stresses such as bronchopulmonary dysplasia and necrotizing enterocolitis.