Journal of Lipid Research, Vol 28, 152-161, Copyright © 1987 by Lipid Research, Inc.
Pantethine inhibits cholesterol and fatty acid syntheses and stimulates carbon dioxide formation in isolated rat hepatocytes
G Cighetti, M Del Puppo, R Paroni, E Fiorica and M Galli Kienle
The effects of pantethine on cholesterol and fatty acid metabolism were
investigated in isolated rat hepatocytes. Preincubation of the cells with
pantethine induced a concentration-dependent decrease of the radioactivity
incorporated into carbon dioxide and lipids in incubations with
[2-14C]acetate. When pantethine and the labeled substrate were
simultaneously added to the cell suspension, there was an enhancement of
carbon dioxide radioactivity at short incubation time (5 min) whereas, at
longer incubation time, values were comparable to those of controls; lipid
radioactivity, instead, was dramatically reduced by pantethine even at
short incubation time and decreased further during the incubation, being
23% of that of controls at 60 min. Analysis of the incubation medium showed
that pantethine induced a concentration- and time-dependent release of
acetate into the medium. Results of the effect of the acetate concentration
on the incorporation of [2-14C]acetate radioactivity into CO2 and lipids in
control hepatocytes allowed the conclusion that the above-described
modifications induced by pantethine are only partially attributable to the
dilution of the labeled substrate, and that catabolism of acetate to carbon
dioxide is stimulated by the disulphide pantethine, whereas cholesterol and
fatty acid syntheses are inhibited.
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