Generation of hydroxytrimethyllysine from trimethyllysine limits the carnitine biosynthesis in premature infants.

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.