l-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2

Abstract

Maternofetal transport of l-carnitine, a molecule that shuttles long-chain fatty acids to the mitochondria for oxidation, is thought to be important in preparing the fetus for its lipid-rich postnatal milk diet. Using brush-border membrane (BBM) vesicles from human term placentas, we showed that l-carnitine uptake was sodium and temperature dependent, showed high affinity for carnitine (apparent K(m) = 11.09 +/- 1.32 microM; V(max) = 41.75 +/- 0.94 pmol.mg protein(-1).min(-1)), and was unchanged over the pH range from 5.5 to 8.5. l-Carnitine uptake was inhibited in BBM vesicles by valproate, verapamil, tetraethylammonium, and pyrilamine and by structural analogs of l-carnitine, including d-carnitine, acetyl-d,l-carnitine, and propionyl-, butyryl-, octanoyl-, isovaleryl-, and palmitoyl-l-carnitine. Western blot analysis revealed that OCTN2, a high-affinity, Na(+)-dependent carnitine transporter, was present in placental BBM but not in isolated basal plasma membrane vesicles. The reported properties of OCTN2 resemble those observed for l-carnitine uptake in placental BBM vesicles, suggesting that OCTN2 may mediate most maternofetal carnitine transport in humans.

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…The incidence of FAO disorders in the Chinese population could be even higher if we included the false-negative cases. For example, CUD can only be detected by NBS in half of affected newborns because of carnitine transportation through the placenta from the mother (Wilcken et al 2001;Lahjouji et al 2004). CUD disease severity decreased in patients detected by NBS.…”

“…As we have discussed in the previous section, newborns with CUD can be missed by NBS because of normal free carnitine levels at birth (Wilcken et al 2001;Lahjouji et al 2004). A looser cut-off value can increase the sensitivity of the tests, but will also increase the rate of false-positives.…”

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

“…All organisms have enzymatic and nonenzymatic mechanisms to scavenge oxidants, or to repair damage caused by reactive oxygen species. Oxygen species are known to cause oxidative damages to macromolecules (Lahjouji et al 2004). Chemical compounds and reactions capable of generating potential toxic oxygen species/free radicals are referred to as prooxidants.…”

“…L-carnitine is an essential cofactor in the β-oxidation of long-chain fatty acids. It is also believed to be important for acting as an acyl group acceptor in order to maintain sufficient cellular levels of free coenzyme A (CoA) and may act as an osmo protectant in organs such as the kidney and as a general cell membrane stabilizer (Lahjouji et al 2004;Biolo et al 2008).…”

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

“…It also regulates acetyl storage and transfer in mitochondria, cells, and between organs, and the transport of potentially toxic, activated acids out of mitochondria (Bellinghieri et al, 2003). LC is believed to be important for acting as an osmo protectant in organs such as the kidney, and as a general cell membrane stabilizer (Lahjouji et al, 2004;Biolo et al, 2008). LC homeostasis is maintained by a modest biosynthesis in the liver and kidney, absorption from dietary sources (eg, meat and dairy products), and efficient renal tubular reabsorption from glomerular filtrate (Rebouche, Seim 1998).…”