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Generation of hydroxytrimethyllysine from trimethyllysine limits the carnitine biosynthesis in premature infants
Insights
Oral administration of epsilon-N-Trimethyl-L-lysine (TML) to premature infants showed increased TML levels. The conversion of TML to hydroxy-TML appears to be a regulatory step in neonatal carnitine biosynthesis.
Area of Science:
- Biochemistry
- Neonatal Metabolism
- Nutritional Science
Background:
- Carnitine is essential for fatty acid metabolism in neonates.
- The biosynthesis pathway of carnitine in premature infants is not fully elucidated.
- epsilon-N-Trimethyl-L-lysine (TML) is a precursor in carnitine biosynthesis.
Purpose of the Study:
- To investigate the metabolic fate of orally administered TML in premature infants.
- To identify regulatory steps in neonatal carnitine biosynthesis.
- To assess the impact of TML dosage on carnitine levels.
Main Methods:
- Oral administration of TML to two groups of premature infants at different dosages.
- Analysis of plasma and urinary carnitine and TML levels.
- 1H NMR and Fast Atom Bombardment Mass Spectrometry (FAB-MS) for metabolite identification.
Main Results:
- Low-dose TML (100 μmol/day) increased urinary TML 17-fold with no change in carnitine.
- High-dose TML (1 mmol) increased plasma and urinary carnitine, and urinary TML 62-fold.
- NMR and FAB-MS confirmed increased TML and no changes in other precursors.
Conclusions:
- The conversion of TML to hydroxy-TML is likely a regulatory step in neonatal carnitine biosynthesis.
- A limitation in the conversion of hydroxy-TML to carnitine is unlikely.
- These findings provide insights into carnitine metabolism in premature infants.
Abstract:
epsilon-N-Trimethyl-L-lysine (TML) was given orally for 1 day to two groups of premature infants. There was no change in the output or plasma levels of carnitine at a dose of 100 mumol/day; however, the urinary TML increased 17-fold. In the second group, administration of 1 mmol TML increased the plasma levels and urinary output of carnitine; the output of TML increased 62-fold. During a search of the metabolites of carnitine biosynthesis by 1H NMR analysis of urine, only one new resonance (corresponding to the TML) could be identified in both groups. Fast atom bombardment mass spectrometry (FAB-MS) analysis of urine samples indicated an increase in TML in the treated patients; no changes were found in the relative abundance of any other precursors. These data show that a significant limitation of the conversion of hydroxy-TML to carnitine is not likely; rather, the conversion of TML to hydroxy-TML is regulatory in neonatal carnitine biosynthesis.