Related Experiment Videos
Compartmentation of endogenously synthesized amino acids in neonates
R G Miller1, T H Keshen, F Jahoor
1Department of Surgery, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
Insights
Limited conversion of glucose to proline, aspartate, and cysteine in premature neonates suggests these amino acids are conditionally essential. Further study revealed distinct intracellular aspartate compartmentation but not proline, indicating proline may be essential for neonates.
Area of Science:
- Biochemistry
- Neonatal Nutrition
- Metabolic Research
Background:
- Premature neonates exhibit limited conversion of D-[U-13C]glucose to proline (Pro), aspartate (Asp), and cysteine (Cys).
- This limited conversion implies these amino acids (AA) may be conditionally essential for this population.
Purpose of the Study:
- To investigate whether limited amino acid synthesis in premature neonates stems from insufficient precursor (glucose) dose or intracellular compartmentation.
- To differentiate between inadequate synthesis and precursor availability or compartmentalization of newly synthesized amino acids.
Main Methods:
- Two phases of intravenous D-[U-13C]glucose infusions (5 mg/kg/min for 4 hr) in premature neonates receiving total parenteral nutrition.
- Measurement of isotopic enrichments in free plasma amino acids and glucose via gas chromatography/mass spectrometry.
- Analysis of isotopic enrichments in amino acids incorporated into hepatically synthesized proteins (fibrinogen, VLDL-apolipoprotein B-100) in phase 2.
Main Results:
- Despite high glucose enrichment (>66%), Pro, Asp, and Cys showed the lowest enrichments among all amino acids (P < 0.05).
- Aspartate exhibited high enrichment in apo B-100, indicating significant intracellular compartmentation (P < 0.001).
- Proline showed low enrichment in free plasma amino acids without evidence of intracellular compartmentation.
Conclusions:
- Limited conversion of glucose to Pro, Asp, and Cys is not due to low precursor glucose enrichment in premature neonates.
- Evidence supports intracellular aspartate compartmentation in premature neonates.
- Low plasma proline enrichment and lack of compartmentation suggest proline is a conditionally essential amino acid for premature neonates.
Abstract:
The conversion of D-[U-13C]glucose to proline (Pro), aspartate (Asp), and cysteine (Cys) is limited in premature neonates, implying that these amino acids (AA) are conditionally essential. This study was performed to determine whether these findings resulted from an insufficient precursor dose or intracellular compartmentation of newly synthesized amino acids, rather than inadequate synthesis. In the first phase of this study, seven total parenteral nutrition-fed, premature neonates received IV D-[U-13C]glucose at 5 mg/kg/min for 4 hr. In the second phase, a separate cohort of eight patients received an identical infusion. Blood was obtained before and at the end of the infusion. Isotopic enrichments of the free plasma AA and glucose were measured using gas chromatography/mass spectrometry in both studies. In phase 2, the isotopic enrichments of the AA bound to the hepatically synthesized proteins, fibrinogen and VLDL-apolipoprotein B-100 (apo B-100), were measured. In phase 1, despite a glucose precursor enrichment greater than 66%, Pro, Asp, and Cys remained the least enriched of all amino acids studied (P < 0.05). Asp, but not Pro, demonstrated very high enrichments in apo B-100 (P < 0.001), reflecting distinct intracellular compartmentation. We conclude that the limited conversion Of D-[U-13C]glucose to Pro, Asp, and Cys did not result from low precursor glucose enrichment and that there is evidence of Asp compartmentation (intracellular) in premature neonates. However, the low Pro enrichment in the free plasma AA pool and the absence of intracellular Pro compartmentation suggest that Pro may be a conditionally essential AA for premature neonates.