Abstract
The topography of formation and migration of phosphatidic acid (PA) in the transverse plane of rat liver mitochondrial outer membrane (MOM) were investigated. Isolated mitochondria and microsomes, incubated with sn-glycerol 3-phosphate and an immobilized substrate palmitoyl-CoA-agarose, synthesized both lyso-PA and PA. The mitochondrial and microsomal acylation of glycerophosphate with palmitoyl-CoA-agarose was 80-100% of the values obtained in the presence of free palmitoyl-CoA. In another series of experiments, both free polymyxin B and polymyxin B-agarose stimulated mitochondrial glycerophosphate acyltransferase activity approximately 2-fold. When PA loaded mitochondria were treated with liver fatty acid binding protein, a fifth of the phospholipid left the mitochondria. The amount of exportable PA reduced with the increase in the time of incubation. In another approach, PA-loaded mitochondria were treated with phospholipase A(2). The amount of phospholipase A(2)-sensitive PA reduced when the incubation time was increased. Taken together, the results suggest that lysophosphatidic acid (LPA) and PA are synthesized on the outer surface of the MOM and that PA moves to the inner membrane presumably for cardiolipin formation.
Highlights
Phosphatidic acid (PA),1 the key intermediate in the biosynthetic pathway of glycerolipids, is synthesized by two successive acylations of glycerol 3-phosphate [1]
The results suggest that lysophosphatidic acid (LPA) and PA are synthesized on the outer surface of the mitochondrial outer membrane (MOM) and that PA moves to the inner membrane presumably for cardiolipin formation
For both mitochondria and microsomes, their activities of glycerophosphate acyltransferase (GAT) is over 90% in the presence of immobilized substrate when compared with the activities in presence of free palmitoyl-CoA
Summary
Phosphatidic acid (PA), the key intermediate in the biosynthetic pathway of glycerolipids, is synthesized by two successive acylations of glycerol 3-phosphate [1]. The acylation steps are carried out by glycerophosphate acyltransferase (GAT) [2] and monoacylglycerolphosphate acyltransferase (MGAT) [3]. In mammalian cells, these enzymes are located in both MOM and endoplasmic reticulum (4 – 6). Several lines of evidence suggest that the mitochondrial GAT regulates the selective positioning of saturated fatty acids at the sn-1 position of glycerophospholipids. Recent experiments from different laboratories suggest that the activity of mitochondrial GAT can change under different physiological [18, 19] and nutritional conditions [20, 21] and in the presence of some metabolic modulators [22]. Cloning and sequencing of the cDNA (GenBankTM accession number U36771) revealed the presence of two transmembrane regions [12], supporting the biochemical observation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
