VOL.
6,
NO.
5,
MAY
1967
Hydroxylation of r-Butyrobetaine to Carnitine in Rat Liver* Goran Lindstedt
y-Butyrobetaine (4-trimethylaminobutyric acid) was hydroxylated to carnitine (3-hydroxy-4trimethylaminobutyric acid) by a partially purified soluble protein fraction from rat liver. The reaction, which required molecular oxygen and ferrous ion, was stimulated by a combination of ascorbate and a reduced nicotinamide-adenine dinucleotide phosphate regenerating system, and also by catalase and by liver microsomes. Significant enrichment of tritium in ybutyrobetaine was obtained when [carboxy- 14C-2,33H]y-butyrobetaine had been used as substrate, indicating a kinetic hydrogen isotope effect. Homogenates ABSTRACT:
T
he biosynthesis of carnitinel is still largely unknown. The low incorporation of radioactivity from methyl-labeled methionine into carnitine indicates that carnitine is formed in rats at a slow rate (Wolf and Berger, 1961 ; Bremer, 1961; Strength and Yu, 1962). The formation of carnitine from y-butyrobetainel in rats and mice has been demonstrated previously (Lindstedt and Lindstedt, 1961, 1965a; Bremer, 1962) and results from preliminary experiments with preparations from rat liver indicated an oxygenase mechanism for this conversion (Lindstedt and Lindstedt, 1962). The present paper shows that the hydroxylation of y-butyrobetaine is catalyzed by a soluble protein fraction from rat liver. The reaction requires molecular oxygen and ferrous ion and is stimulated by ascorbate and a NADPH-regenerating system. The high substrate specificity of the enzyme and the capacity for carnitine formation may indicate that y-butyrobetaine is a physiologic precursor of carnitine.
* From the Department of Chemistry, I
