MOLECULAR-CLONING AND CHARACTERIZATION OF HIGH-AFFINITY CARNITINE TRANSPORTER FROM RAT INTESTINE

Carnitine is an essential component for mitochondrial beta-oxidation o f fatty acid. Using the degenerate primers designed for organic anion transporters and an organic cation transporter, we isolated a novel cD NA encoding a carnitine transporter (CT1) from rat intestine. CT1 enco des a 557-amino-acid protein with 12 putative membrane-spanning domain s. When expressed in Xenopus oocytes, CT1 mediated a high-affinity tra nsport of L-carnitine (K-m = 25 mu M). The replacement of extracellula r sodium with Li reduced CT1-mediated L-carnitine uptake to 19.8%. CT1 did not transport typical substrates for either organic anion or orga nic cation transporters, such as p-aminohippurate and tetraethylammoni um. Octanoylcarnitine, acetylcarnitine, and gamma-butyrobetaine showed potent inhibitory effects on CT1-mediated L-carnitine uptake; betaine and D-carnitine showed moderate inhibition. CT1 mRNA was strongly exp ressed in the testis, colon, kidney, and liver and weakly in the skele tal muscle, placenta, small intestine, and brain. No CT1 expression wa s detected in the heart, spleen, or lung. The present study provides t he molecular basis of carnitine transport in the body. (C) 1998 Academ ic Press.