No replenishment of carnitine from trimethyllysine during pivalate-induced carnitine loss in humans

Abstract

Pivaloylcarnitine formation from exogenous carnitine and from carnitine precursor 6-N-trimethyllysine was investigated in two groups of pivampicillin treated subjects. In the first group, medication of pivampicilin led to the formation of and urinary excretion of pivaloylcarnitine. Oral L-carnitine supplementation, introduced after the third day of treatment, caused 2 fold urinary excretion of carnitine esters. For this group, the plasma levels and urinary output of butyrobetaine also decreased on the third day of pivampicillin treatment, but it normalized after carnitine administration. In contrast, urinary output of the carnitine precursor, trimethyllysine did not change during the study period. For the second group, oral trimethyllysine supplementation was started on the 4th day of pivampicillin treatment. Administration of trimethyllysine had no effect on the urinary output of carnitine esters, although the urinary excretion of it increased from approximately 25 to 450 μmol/day. Plasma levels and urinary output of butyrobetaine decreased during the pivampicillin treatment and administration of trimethyllysine did not restore the levels. Administration of trimethyllysine produced a large increase in urinary trimethyllysine output, but it did not affect the fast atom bombardment mass spectrometry signal intensity of other carnitine precursors. The urinary metabolite profile shows, that the conversion process of trimethyllysine to hydroxy-trimethyllysine represent and obstacle in butyrobetaine and carnitine biosynthesis in humans in vivo. Because the administered trimethyllysine was not converted to carnitine or carnitine precursors to any significant extent, its nutritional value with respect to the replenishment of carnitine reserves is questionable.