gamma-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant.

Carnitine biosynthesis was assessed in human infants by measuring changes in plasma carnitine concentration and rates of urinary carnitine excretion after infants were fed carnitine-free formulas with and without added epsilon-N-trimethyl-L-lysine or gamma-butyrobetaine. This study was undertaken to test the hypothesis that carnitine biosynthesis in the human infant is regulated by substrate availability rather than activity of gamma-butyrobetaine hydroxylase, the final enzyme in the carnitine biosynthetic pathway. Ten infants were fed carnitine-free formula supplemented with either 500 microM epsilon-N-trimethyl-L-lysine or 500 microM gamma-butyrobetaine for 14 d. Plasma carnitine concentration and rate of urinary carnitine excretion were measured in infants before and after this period. Plasma carnitine concentration increased twofold when infants were fed either epsilon-N-trimethyl-L-lysine and increased threefold when infants were fed gamma-butyrobetaine. The rate of carnitine excretion doubled when infants were fed epsilon-N-trimethyl-L-lysine and increased 30-fold when infants were fed gamma-butyrobetaine. Absorption of epsilon-N-trimethyl-L-lysine was verified by demonstrating increased urinary excretion of epsilon-N-trimethyl-L-lysine in infants fed this substrate. We conclude that gamma-butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant. Development of renal and hepatic gamma-butyrobetaine hydroxylase activity was determined in necropsy tissue from individuals of various ages. It was verified that gamma-butyrobetaine hydroxylase activity is developmentally regulated in the liver, but not in the kidney. The clinical relevance of this observation is diminished in view of the results of the in vivo studies of carnitine biosynthesis in infants.