Sodium gradient-stimulated transport of l-carnitine into renal brush border membrane vesicles: Kinetics, specificity, and regulation by dietary carnitine

• Published in: Archives of biochemistry and biophysics Vol. 235; no. 2; pp. 393 - 402
• Main Authors: Rebouche, Charles J., Mack, Diane L.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.12.1984; Elsevier
• Subjects: Animals; Biological and medical sciences; Biological Transport; Carnitine - metabolism; Carnitine - pharmacology; Cell physiology; Diet; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; In Vitro Techniques; Kidney - metabolism; Kinetics; Male; Membrane and intracellular transports; Microvilli - metabolism; Molecular and cellular biology; Rats; Sodium - physiology; Temperature; Osmotic gradient; Rat; Rodentia; Cofactor; Kidney; Carnitine; Vertebrata; Brush border; Regulation(control); Mammalia; Sodium; Membrane transport; Plasma membrane; Kinetic parameter
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/0003-9861(84)90212-1

l-Carnitine transport by rat renal brush border membrane vesicles was stimulated by a Na + gradient (extravesicular > intravesicular). Total carnitine entry was 2.7 and 3.2 times higher at 15 s in the presence of a 100 m m NaCl gradient than when the vesicles were incubated isoosmotically in buffered 100 m m KCl or buffered mannitol, respectively. Specific carnitine transport (total entry minus contribution from diffusion) was stimulated 3.6- and 5.7-fold, respectively. An “overshoot” was observed for total carnitine entry in the presence of a Na + gradient but not in the presence of a K + gradient or in the absence of an ion gradient. l-Carnitine transport was saturable. K T and V max for total carnitine transport were 0.11 m m and 11.6 pmol s −1 mg protein −1, respectively, and for Na +-gradient-dependent carnitine transport, 0.055 m m and 5.09 pmol s −1 mg protein −1, respectively. The transport process was structure-specific for a quaternary nitrogen and carboxyl groups attached by a 4- to 6-carbon chain, but without other charged functional groups. Other evidence for a carrier-mediated process included trans-stimulation of transport by intravesicular carnitine and a peak of activity at near physiological temperature. Kinetic data derived from this study, coupled with data from previous physiological studies from this laboratory, suggests that carnitine transport by the brush border membrane is not limiting for carnitine reabsorption. Dietary carnitine (1% of diet for 10 days) reduced by 52% the rate of carnitine transport across the brush border membrane in vitro, without affecting rates of d-glucose, l-lysine, l-glutamic acid, or l-alanine transport. Down-regulation of carnitine transport may prevent excessive or toxic accumulation of l-carnitine in renal tubular cells exposed to high extracellular carnitine concentrations.