Butyrobetaine availability in liver is a regulatory factor for carnitine biosynthesis in rat: flux through butyrobetaine hydroxylase in fasting state

Urinary excretion of total carnitine in 48-h fasted rats dropped to 0.30 ± 0.01 μmol/day from 2.23 ± 0.4 μmol/day found in fed, control animals (mean ± SEM). Despite this marked retention, the total carnitine content of the whole body remained constant, about 83 μmol, predicting a slow-down in biosynthesis. The conversion of butyrobetaine into carnitine takes place only in the liver in rats. 48 h of starvation caused a decrease in the liver butyrobetaine level from 11.6 ± 1.19 nmol/g to 9.30 ± 1.19 nmol/g, which in whole livers corresponds to a decrease from 138 nmol to 61.3 nmol. The conversion rate of butyrobetaine into carnitine was studied with radiolabelled butyrobetaine. 30 min after injection of [3H]butyrobetaine the carnitine pool in the liver of fasted rats was labelled to about the same extent as that in fed rats, but from a butyrobetaine pool with higher specific radioactivity. Therefore, the conversion rate of butyrobetaine into carnitine was reduced. The newly formed carnitine found in the whole body of fasted rats was estimated to be 59% of controls. We conclude that the biosynthesis of carnitine in fasted rats slows down, for which a decreased availability of butyrobetaine in the liver is responsible. Urinary excretion of butyrobetaine in the fasted group decreased to 74.1 nmol/day from the 222-nmol/day control value while the butyrobetaine content of whole body did not significantly decrease (2.85 μmol vs. 3.04 μmol). Urinary excretion of trimethyllysine was also depressed.