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PubMed · 16826461

Involvement of recognition and interaction of carnitine transporter in the decrease of L-carnitine concentration induced by pivalic acid and valproic acid.

Noboru Okamura·Shuichi Ohnishi·Hiroyuki Shimaoka·Ryo Norikura·Hiroshi Hasegawa
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Abstract

PURPOSE: Prodrugs with pivalic acid and valproic acid decrease L-carnitine concentration in plasma and tissues by urinary excretion of acylcarnitine as pivaloylcarnitine (PC) and valproylcarnitine (VC), respectively. We investigated the role of the Na+/L-carnitine cotransporter in the porcine kidney epithelial cell line, LLC-PK1 for the decrease of L-carnitine concentration. METHODS: The uptake of L-[3H]carnitine, acetyl-L-[3H]carnitine (AC), L-[3H]PC and L-[3H]VC were investigated in LLC-PK1 cells seeded in a 6-well culture plate. RESULTS: L-Carnitine and AC uptake in LLC-PK1 cells exhibited Na+ dependency. The Km values for L-carnitine and AC uptake were 11.0 and 8.18 microM, respectively. These results indicated expression of Na+/ L-carnitine cotransporter in LLC-PK1 cells. PC and VC inhibited Na+/L-carnitine cotransporter in the competitive (Ki = 90.4 microM) and noncompetitive (Ki = 41.6 microM) manners, respectively. PC and VC uptake by Na+/L-carnitine cotransporter were not observed in LLC-PK1 cells. CONCLUSIONS: These data suggested that PC and VC formed in the body could not be reabsorbed in the kidney, resulting in the decrease of L-carnitine concentration. In addition, inhibition of L-carnitine reabsorption by VC with lower Ki value could induce the decrease of L-carnitine concentration. Collectively, the recognition and interaction of Na+/L-carnitine cotransporter are important factors for carnitine homeostasis.

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AcetylcarnitineAlgorithmsAmino Acid Transport Systems, BasicAnimalsBiological Transport, ActiveCarnitineCarrier ProteinsEnzyme InhibitorsLLC-PK1 CellsPentanoic AcidsSwineValproic AcidJournal Article

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Noboru Okamura, Shuichi Ohnishi, Hiroyuki Shimaoka, Ryo Norikura, Hiroshi Hasegawa. 2006. Involvement of recognition and interaction of carnitine transporter in the decrease of L-carnitine concentration induced by pivalic acid and valproic acid.. https://doi.org/10.1007/s11095-006-9002-9

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