L-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2.
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.
Lahjouji
Karim
K
Division of Medical Genetics, Hôpital Sainte-Justine, Université de Montréal, 3175 Côte Sainte-Catherine, Montreal, Quebec, Canada H3T 1C5.
Elimrani
Ihsan
I
Lafond
Julie
J
Leduc
Line
L
Qureshi
Ijaz A
IA
Mitchell
Grant A
GA
D002331:Carnitine / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008871:Microvilli / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012964:Sodium / Q000494:pharmacology; D000074058:Solute Carrier Family 22 Member 5; D013696:Temperature; D014316:Tritium; D015262:Xenobiotics / Q000493:pharmacokinetics
D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D015262:Xenobiotics; D014316:Tritium; D012964:Sodium; D002331:Carnitine