No abstract

Rat hepatocytes were treated with Staphylococcus aureus alpha-toxin to permeabilize their plasma membrane for low-molecular-mass compounds. During incubation with 1 mM labelled fatty acid, phosphatidate and, less clearly, lysophosphatidate rapidly reached a steady state, whereas labelled diacylglycerol accumulated to some extent, at least in the absence of exogenous CDP-choline. Esterification and oxidation were linearly related to the fatty acid concentration, and there was no indication for saturation with acyl-CoA. However, when permeabilized cells were incubated with labelled sn-glycerol 3-phosphate and 1 mM unlabelled fatty acid, glycerolipid synthesis and the level of esterification intermediates reached a plateau between 0.25 and 0.50 mumol of the triose phosphate/ml. The synthesis of phosphatidylcholine was dependent on addition of CDP-choline. In presence of the latter, diacylglycerol no longer accumulated and triacylglycerol synthesis was suppressed, although the sum of synthesized diacylglycerol, triacylglycerol and phosphatidylcholine remained constant. This indicates that the same pool of diacylglycerol is shared by choline-phosphotransferase and diacylglycerol acyltransferase and that the relative activity of these enzymes depends on the CDP-choline supply. Comparison of the levels of the esterification intermediates with the activity of the respective steps of the pathway reveals that, at a fixed fatty acid concentration, glycerophosphate acyltransferase determines the esterification rate, whereas lysophosphatidate acyltransferase and, at low CDP-choline levels, diacylglycerol acyltransferase approach saturation at elevated sn-glycerol 3-phosphate concentration. There is, however, no indication for a regulatory role of phosphatidate phosphohydrolase in this system. The significance of these findings for the regulation of triacylglycerol synthesis under conditions in vivo is discussed.

Drug-induced acanthosis nigricans has been reported in the literature. We present a patient with familial combined hyperlipidemia who developed nicotinic-acid-induced acanthosis nigricans. The literature on the cutaneous side effects of nicotinic acid as well as on the medications that can cause acanthosis nigricans is reviewed. Some hypotheses on the pathogenesis of nicotinic-acid-induced acanthosis are presented.

We present a 43-year-old man who worked in the plastics industry and who suffered from an occupational dermatitis on the hands and forearms. He was found to be allergic to an epoxy silane compound that was contaminated with allyl glycidyl ether, a reactive epoxy diluent. HPLC analysis and patch testing indicated that this impurity was probably the only sensitizer. Moreover, the gloves used provided absolutely no protection, as the inner side also generated strong positive reactions.

Isolated hepatocytes from fed and starved rats, permeabilized with Staphylococcus aureus a-toxin, were incubated with increasing concentrations of radiolabelled fatty acids, in the presence of a saturating concentration of 3-GP. Incorporation of label into LPA, PA and DAG was lower in cells from starved rats than in cells from fed rats, apparently reflecting the lower activity of GPAT after starvation. This enzyme approached saturation at high fatty acid levels and determined the overall flux through the esterification pathway. TAG synthesis, however, was the same in both nutritional states and could not be saturated with fatty acid under the given conditions. Taken together with the observed accumulation of DAG, these data suggest that the rate of TAG synthesis is controlled by the fatty acid supply and, more particularly, by the affkity of DGAT for acyi-CoA.