Production of bis(monoacylglycero)phosphate from phosphatidylglycerol in isolated liver lysosomes of chloroquine-pretreated rats.

Labelled phosphatidylglycerol was incubated with rat liver lysosomes from animals treated for 3 to 20 days with chloroquine diphosphate. The longer the period of pretreatment with the amphiphilic drug, the greater was the increase in the synthesis rate of bis(monoacylglycero)phosphate, both in the absolute values and when related to the lysosomal protein which was also increased. The mechanism of the in vitro conversion of phosphatidylglycerol to bis(monoacylglycero)phosphate was studied by using phosphatidylglycerol labelled with 14C and/or 3H in different positions of the molecule. Assays with rac-1-(1,2-diacyl-[2-3H]glycero-3-phospho)-[U-14C]glycerol clearly demonstrated that the 3H/14C ratio of the substrate was the same as found in the product bis(monoacylglycero)phosphate. Therefore the whole glycerophosphoglycerol backbone of the substrate is used for bis(monoacylglycero)phosphate formation, and recombination of released glycerol moieties can be excluded. Experiments with phosphatidylglycerol labelled in both fatty acids suggest that only one acyl group of the substrate is preserved in bis(monoacylglycero)-phosphate. The analysis of further products formed during incubations of rat liver lysosomes with labelled phosphatidylglycerol showed a rapid degradation of the glycerolipid mainly by the action of phospholipase A and C.