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Formation of pivaloylcarnitine in isolated rat heart cells

, : Formation of pivaloylcarnitine in isolated rat heart cells. Biochimica Et Biophysica Acta. 1259(2): 161-165

Pivaloyl-containing antibiotics and pivalic acid in man or rat have been reported to cause increased urinary carnitine loss secondary to pivaloylcarnitine generation. Pivaloylcarnitine concentration was especially high in heart after administration of pivalic acid or pivampicillin in vivo. Formation of pivaloylcarnitine was therefore studied in isolated rat heart cells in the presence of sodium pivalate. Formation of pivaloylcarnitine in rat heart cells increased with incubation time, after a lag time from 0 to 2 h and linearly up to 6 h. The formation increased with increasing concentration of sodium pivalate, followed Michaelis-Menten kinetics with an apparent K-m = 348 +- 10 mu-M and V-max = 116 +- 20 pmol cntdot mg protein-1 cntdot h-1. Bromoacetylcarnitine inhibited the pivaloylcarnitine formation to K-i = 116 +- 43 mu-M and V-max = 107 +- 14 pmol cntdot mg protein-1 cntdot h-1. The uptake of carnitine in heart cells was suppressed 62-74% by deoxycarnitine (40 mu-M) and D-carnitine (200 mu-M), and 95% by NaF (5 mM), NaN-3 (500 mu-M) or at temperature 4 degree C. Pivaloylcarnitine inhibited carnitine uptake to 33-35% of the controls, while sodium pivalate did not. More than 90% of intracellular pivaloylcarnitine was released from the heart cells after 18 h of incubation in the absence of sodium pivalate and L-carnitine. These data show that pivalate is readily converted to pivaloylcarnitine in heart cells, in contrast to the limited conversion in hepatocytes.


PMID: 7488636

DOI: 10.1016/0005-2760(95)00151-2

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