Abstract
We have previously reported that valproate (VAL) reduced coenzymeA (CoA) and acetyl CoA (AcCoA) levels in the livers (LV) of 4-8-d-old mice. In this study, we attempted to increase LV CoA and AcCoA synthesis in normal mice by s.c. injection of pantothenate (B5, 2 mmol/kg), L-cysteine (CYST, 1 mmol/kg) and L-carnltlne (CARN, 2.5 mmol/kg). Effects in VAL-treated mice were also examined. B5 + CYST + CARN had a significant effect on LV CoA metabolism in normal mice (Table). B5 + CYST without CARN or CARN alone had no effect. In VAL-treated mice (15 mg/kg) (N=6) injection of B5 + CYST + CARN increased depressed LV CoA and AcCoA levels 58% (P<0.001), and 70% (P=0.006), respectively; plasma [p-OHB] increased 128%, P<0.001.
CoA and AcCoA are essential cofactots in over 100 synthetic and degradative reactions. Increasing levels of CoA and AcCoA In LV may have clinical relevance not only to VAL-associated hepatotoxicity, but also to other conditions where there is sequestration of CoA (as acyl-CoA) and inhibition of LV metabolism because of CoA and AcCoA depletion.
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Thurston, J., Hsuhart, R. A SINGLE DOSE OF PANTOTHENATE, CYSTEINE, AND CARNITINE INCREASES LIVER COENZYME A AND ACETYL CoA LEVELS IN NORMAL INFANT MICE AND SUBSTANTIALLY REVERSES VALPROATE-INDUCED HEPATIC DYSFUNCTION: POSSIBLE CLINICAL SIGNIFICANCE. Pediatr Res 21 (Suppl 4), 342 (1987). https://doi.org/10.1203/00006450-198704010-01051
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DOI: https://doi.org/10.1203/00006450-198704010-01051