Site of Carnitine Biosynthesis in the Rat

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Abstract
A series of 3-month-old rats fed a 20% wheat gluten diet limiting in lysine and carnitine was injected intraperitoneally with ε-N-[Me-3H]trimethyl-L-lysine, an efficient precursor of γ-butyrobetaine and carnitine. The rats were subsequently killed at 2-, 6-, 12-, and 24-hour intervals, and the radioactivity in biosynthesized carnitine and γ-butyrobetaine was determined after the isolation of these metabolites by ion-exchange chromatography from various tissue extracts including liver, kidney, skeletal muscle, heart, testis, and plasma. At 2 hours, the specific activity of carnitine in the liver and plasma was the highest and then decreased with time as the specific activity of skeletal muscle, heart, and testis increased concomitantly. The level of carnitine in the kidney remained relatively constant indicating continual turnover. At 2 hours, γ-butyrobetaine was higher in the kidney and heart than in the liver and plasma, but it decreased in all tissues with time. The results were interpreted to mean that all the tissues form γ-butyrobetaine from ε-N-trimethyllysine but then transport it to the liver for conversion to carnitine. This view was supported in other studies of carnitine biosynthesis involving intratesticular injection of ε-N-trimethyllysine or γ-buty-robetaine, but were consistent with current work in this laboratory discussed herein, that although the liver is the primary site of carnitine biosynthesis, the testis has a limited capacity for such synthesis.

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