N 6-Trimethyl-lysine metabolism. 3-Hydroxy-N6-trimethyl-lysine and carnitine biosynthesis

Abstract

Rats injected with N6-[Me-3H]trimethyl-lysine excrete in the urine 5 radioactively labeled metabolites. Of these identified metabolites 2 are carnitine and 4-trimethylammoniobutyrate. A 3rd metabolite, identified as 5-trimethylammoniopentanoate, is not an intermediate in the biosynthesis of carnitine; the 4th and major metabolite, N2-acetyl-N6-trimethyl-lysine, is not a precursor of carnitine. The remaining metabolite (3-hydroxy-N6-trimethyl-lysine) is converted into trimethylammoniobutyrate and carnitine by rat liver slices and into trimethylammoniobutyrate by rat kidney slices. In rat liver and kidney-slice experiments, radioactivity from DL-N6-trimethyl-[1-14C]lysine and DL-N6-trimethyl[2-14C]lysine was incorporated into N2-acetyl-N6-trimethyl-lysine and 3-hydroxy-N6-trimethyl-lysine, but not into trimethylammoniobutyrate or carnitine. A procedure was devised to purify milligram quantities of 3-hydroxy-N6-trimethyl-lysine from the urine of rats injected chronically with N6-trimethyl-lysine (100 mg/kg body wt/day). The structure of 3-hydroxy-N6-trimethyl-lysine was confirmed chemically and by NMR spectrometry. The sequence for carnitine biosynthesis in liver is: N6-trimethyl-lysine .fwdarw. 3-hydroxy-N6-trimethyl-lysine .fwdarw. .fwdarw. 4-trimethylammoniobutyrate .fwdarw. carnitine.