Lysosomal Bis(monoacylglycero)phosphate of Rat Liver, its Induction by Chloroquine and its Structure

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Abstract
Since chloroquine is able to induce phospholipidosis, and in particular formation of bis(monoacylglycero)phosphate [(MAG)2P] in rat liver lysosomes, the influence of the drug on this acidic phospholipid was tested after application of the drug for different periods, 3, 7, 14, 21 and 28 days, and after application of different doses of the drug for 7 days. In both cases, amounts of total phospholipids and of (MAG)2P within lysosomal lipids showed a direct relationship to quantity of the drug. Lysosomal fractions were identified by acid phosphatase [EC 3.1.3.2] activity and by EM. After 14 days of treatment, the lysosomal fractions showed an increase in the marker enzyme to more than 30 times the level in the homogenate and consisted of almost pure lamellar bodies. (MAG)2P was isolated from those lysosomal lipid fractions by column chromatography. We also isolated this phospholipid from tritosomal lipids and tested the 2 preparations in different ways. They both showed glycerophosphoglycerol as the only P-containing product after mild alkaline hydrolysis, and molar ratios for phosphorus: fatty acid: glycerol close to 1:2:2; and yielded diacetylacyl glycerol after acetolysis. (MAG)2P apparently occurs in these secondary lysosomes, and its production is a consequence of the accumulation of lysosomes. There is some indication for the occurrence of an acylated (MAG)2P (which is the same as acylphosphatidylglycerol) within the same cell organelles.