Biosynthesis of carnitine and 4-N-trimethylaminobutyrate from 6-N-trimethyl-lysine

Abstract

The conversion of 6-N-[Me-(14)C]trimethyl-lysine into carnitine and 4-N-trimethylaminobutyrate (butyrobetaine) was demonstrated in rats kept on a lysine-deficient diet. After the rats were given [(14)C]trimethyl-lysine for 4 days, a total of 17% of the injected label was recovered as carnitine from carcass and urine extracts. Another 8% of the trimethyl-lysine label was converted into 4-N-trimethylaminobutyrate, most of which was recovered from the urine. The conversion of trimethyl-lysine into the above two metabolites supports the pathway of carnitine biosynthesis as lysine+methionine --> 6-N-trimethyl-lysine --> 4-N-trimethylaminobutyrate --> carnitine. In addition, three other metabolites representing 2% of the injected dose were recovered. Only an insignificant portion of the label was recovered as free trimethyl-lysine from the carcass, whereas 22% of the injected label was recovered in the urine. A relatively low specific radioactivity in carnitine was found when 5-N-[Me-(14)C]trimethylaminopentanoate and 6-N-[Me-(14)C]trimethylaminohexanoate were administered to rats in amounts similar to the [(14)C]trimethyl-lysine, suggesting that they were not free intermediates.

Plasma L‐carnitine concentration in healthy dogs and dogs with hepatopathy

“…D‐ and L‐Carnitine can be distinguished, but the metabolically active form is L‐carnitine 2. L‐Carnitine is synthesized from the amino acids lysine and methionine 3,4. The synthesis consists of 5 steps and occurs in the liver of most species, including dogs 5,6.…”

Vitamin C Is Not Essential for Carnitine Biosynthesis in Vivo: Verification in Vitamin C-Depleted Senescence Marker Protein-30/Gluconolactonase Knockout Mice

“…8) Carnitine is synthesized ultimately from the amino acids lysine and methionine. [9][10][11][12][13][14] In some proteins (histones, myosin, calmodulin, and actin), lysine residues are trimethylated on the 4-amino group by specific methyltransferases that use S-adenosyl-L-methionine as the methyl donor 15) (Fig. 1).…”

Canine hereditary ceroid‐lipofuscinosis: Evidence for a defect in the carnitine biosynthetic pathway

“…Free TML, once released from a protein, is converted by the actions of 4 enzymes through a series of 3 metabolic intermediates to carnitine (Fig. 1) [Cox and Hoppel, 1973;Hochalter and Henderson, 1976;Hoppel et al, 1980;Dunn et al, 1984;Davis, 1990;Rebouche, 19911. A defect in any of the enzymes in the carnitine biosynthetic pathway could result in a n accumulation of the intermediates of the pathway preceding the defective enzyme.…”