Detergent solubilization of liver microsomal acyl-coenzyme A:1-acyl-glycerophosphocholine acyltransferase in nephrotic rat.

Hyperlipidaemia is a common feature of nephrotic syndrome and this has been thought to involve increased assembly and secretion of very low density lipoprotein (VLDL) in the liver. An important pathway for an indirect modulation of VLDL. Synthesis is the reaction catalyzed by the acyl-coenzyme A:1-acyl-glycero-phosphcholine acyl transferase. We therefore investigated the activity of this enzyme in liver microsomes isolated from puromycin amino nucleoside induced nephrotic rats. When oleoyl-CoA was employed as the acyl-donor, our results indicated that both the total and detergent soluble enzyme activities (112.2 +/- 16.7; 116.1 +/- 17.5 units, respectively) were significantly higher than the corresponding control levels of 91.1 +/- 11.1 and 75.4 +/- 20.9 units respectively. The percentage stimulation by sodium cholate were 176.5 and 192.2 for the control and nephrotic rats, respectively. In absence of sodium cholate, when oleoyl CoA was replaced by arachidonoyl-CoA as acyl-donor, the measured total enzyme activity was only significantly reduced in the control rats (71.1 +/- 8.9 Vs 91.1 +/- 11.1 Units). Oleoyl-CoA as acyl-donor gave higher values for the soluble and residual enzyme activities (90.4 13.3; 99.5 34.5 unit) than the corresponding control levels (75.9 +/- 10.0; 50.5 +/- 34.0 units) as compared to arachidonoyl-CoA. In the control group the difference was only significant in the residual activity (92.9 20.5 Vs 64.7 24.1 units). The addition of monomethylethanomine (200 mM) had little or no effect, while both reduced glutathione (10 mM) and 1,2-diacylglycerol (1 mM) caused significant reduction in measured activity. These results indicated that in nephrotic rats new phospholipid synthesis is enhanced and this could contribute to the increased VLDL assembly and secretion usually associated with nephrotic syndrome.