Functional characterization of the carnitine transporter defective in primary carnitine deficiency

Primary carnitine deficiency is an autosomal recessive disorder caused by d efective carnitine transport which impairs fatty acid oxidation and manifes ts as nonketotic hypoglycemia or skeletal or heart myopathy. Here we report the functional characterization of this transporter in human fibroblasts. Carnitine enters normal cells by saturable and unsaturable routes, the latt er corresponding to Na+-independent uptake. Saturable carnitine transport w as absent in cells from patients with primary carnitine deficiency. In cont rol cells, saturable carnitine transport was energized by the electrochemic al gradient of Na+. Carnitine uptake was not inhibited by amino acid substr ates of transport systems A, ASC, and X-AG(-), but was inhibited competitiv ely (in potency order) by butyrobetaine > carnitine > palmitoylcarnitine = acetylcarnitine > betaine. Carnitine uptake was also noncompetitively inhib ited by verapamil and quinidine, inhibitors of the multidrug resistance fam ily of membrane transporters, suggesting that the carnitine transporter may share a functional motif with this class of transporters. A high-affinity carnitine transporter was present in kidney 293 cells, but not in HepG2 liv er cells, whose carnitine transporter had a K-m in the millimolar range. Th ese result indicate the presence of multiple types of carnitine transporter s in human cells. (C) 1999 Academic Press.