Hydroxylation of γ‐butyrobetaine to carnitine in human and monkey tissues

Carnitine serves as a carrier of acyl groups into and out of mitochondria and hence is considered to have a central function in the metabolic utilization and synthesis of fatty acids [l-4]. In the rat, the species most extensively studied, adipose tissue, heart, kidney and skeletal muscle catalyze the entire sequence of reactions from e-N-trimethyl-L-lysie to r-butyrobetaine; the same tissues, however, are reported not to hydroxylate the latter compound to carnitine [5-81. Indeed, several studies suggested that the liver is the primary site of carnitine biosynthesis, and that the testis is a secondary site with much less capacity for such synthesis [6-91. In fact it has been considered that extrahepatically synthesized y-butyrobetaine is converted to carnitine exclusively in the liver, and that the carnitine so formed is rapidly transported to other organs [7,10]. That species differences may exist in tissue localization of carnitine synthesis was evidenced by the finding that, in the sheep, kidney and muscle tissues have significant capacity to hydroxylate y-butyrobetaine, albeit relatively low as compared with liver (11). More recently, crude extracts from kidneys of cat, hamster, rabbit, and a single Rhesus monkey were shown to convert y-butyrobetaine to camitine [ 12,131. In those species, the levels of y-butyrobetainehydroxylating activity in kidney nearly equaled or exceeded that measured in the corresponding liver. In contrast, dog, guinea pig, mouse and rat kidney exhibited little or no capacity to hydroxylate y-butyrobetaine. In this study, in which additional primate species