Ascorbic acid and carnitine biosynthesis

It has been suggested that early features of scurvy (fatigue and weakness) may be attributed to carnitine deficiency. Ascorbate is a cofactor for two α-ketoglutarate-re-quiring dioxygenase reactions (ϵ-N-trimethyllysine hydroxylase and 7-butyrobetaine hydroxylase) in the pathway of carnitine biosynthesis. Carnitine concentrations are variably low in some tissues of scorbutic guinea pigs. Ascorbic acid deficiency in guinea pigs resulted in decreased activity of hepatic γ-butyrobetaine hydroxylase and renal but not hepatic ϵ-N-trimethyllysine hydroxylase when exogenous substrates were provided. It remains unclear whether vitamin C deficiency has a significant impact on the overall rate of carnitine synthesis from endogenous substrates. Nevertheless, results of studies of enzyme preparations and perfused liver in vitro and of scorbutic guinea pigs in vivo provide compelling evidence for participation of ascorbic acid in carnitine biosynthesis.