title: Labeled trimethyllysine load depletes unlabeled carnitine in premature infants without evidence of incorporation.
abstract: 6-N-Trimethyl-[d9]-L-lysine (dTML), the labeled form of a mammalian carnitine precursor, was administered to two groups of premature infants. Although the urinary output of dTML significantly increased in the low-dose-treated group (100 micromol/day), this amount did not affect the urinary output or plasma levels of carnitine and carnitine esters. In the second group of infants, after administration of 500 micromol dTML the plasma-free carnitine concentration increased (from 9.95 +/- 0.63 to 12.9 +/- 0.87 nmol/ml, p > 0.05) with a significant increase in the urinary excretion of free carnitine on the day of dTML administration and on the posttreatment day (from 4.79 +/- 1.36 to 9.85 +/- 1.18 and to 17.5 +/- 2.31 micromol/day, respectively). Analysis of urine using fast atom bombardment mass spectrometry (FAB-MS) revealed only the presence of the dTML in the urine of the newborns; no change was detected in the relative abundance of any other carnitine precursor. Surprisingly, in the second group, which received the higher dose of dTML supplement, only the signal intensity of the unlabeled carnitine increased after dTML administration; no new peak appeared in the urine that would correspond to the de novo synthesized carnitine containing the stable isotope-labeled trimethyl group of dTML. Thus, the FAB-MS analysis clearly demonstrated that contrary to the likely prediction, the 270% extra free carnitine output was a consequence of a dose-dependent dTML-induced depletion of the free carnitine reserves from the newborns. The absence of the incorporation of the label from dTML into carnitine strongly suggests that circulating TML is not the precursor of carnitine in premature infants.
authors.affiliation: Department of Pediatrics, University Medical School of Pécs, University Medical School of Pécs, Hungary. meleghb@apacs.pote.hu
authors.forename: B
authors.initials: B
authors.lastname: Melegh
authors.forename: G
authors.initials: G
authors.lastname: Tóth
authors.forename: K
authors.initials: K
authors.lastname: Adamovich
authors.forename: G
authors.initials: G
authors.lastname: Szekely
authors.forename: D A
authors.initials: DA
authors.lastname: Gage
authors.forename: L L
authors.initials: LL
authors.lastname: Bieber
mesh_terms: D002331:Carnitine / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000652:urine; D008297:Male; D011498:Protein Precursors / Q000097:blood; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013997:Time Factors
chemical_list: D011498:Protein Precursors; C003712:trimethyllysine; D008239:Lysine; D002331:Carnitine