Sodium pivalate treatment reduces tissue carnitines and enhances ketosis in rats.
Sodium pivalate, a compound conjugated to carnitine and excreted in the urine was used to induce a secondary carnitine deficiency. In the first series of experiments, rats received in their drinking water either 20 mmol/L sodium pivalate (experimental) or 20 mmol/L sodium bicarbonate (control) for 4 d, 2 wk, or 8 wk. Tissues and urine were collected, and carnitine concentrations in liver, skeletal muscle, heart, plasma and urine were determined. The total carnitine concentrations in tissues and plasma of pivalate-treated rats were significantly depressed (P less than 0.05) at all time points, except at 4 d for skeletal muscle and at 4 d and 2 wk for liver. The acylcarnitine:free carnitine ratios in urine and plasma of the pivalate-treated animals were significantly higher at all time points relative to the controls. In the second experiment, rats received either the pivalate or the bicarbonate treatments for 15 d followed by a 2-d fast. After fasting, the plasma beta-hydroxybutyrate of pivalate-treated rats was significantly higher relative to controls, but there was no significant difference in plasma glucose concentrations. The reduced plasma and tissue carnitine concentrations, increased acylcarnitine:free carnitine ratio in plasma and urine, and fasting ketosis found in pivalate-treated rats are findings also reported for human secondary carnitine deficiency due to organic acidurias.
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48224.
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Bianchi
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Davis
D000818:Animals; D002331:Carnitine / Q000172:deficiency / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D007662:Ketosis / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010421:Pentanoic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D010421:Pentanoic Acids; C005566:pivalic acid; D002331:Carnitine