Regulation of mitochondrial and microsomal phospholipid synthesis by liver fatty acid-binding protein.
Recently we have detected and partially purified a 15-kDa cytosolic L-alpha-lysophosphatidic acid (LPA)-binding protein (LPABP), which stimulates export of LPA from mitochondria (Vancura, A., Carroll, M. A., and Haldar, D. (1991) Biochem. Biophys. Res. Commun. 175, 339-343). Now we have purified this protein to homogeneity. By Western immunoblot analysis, amino acid sequence analysis, and binding characteristics we have shown that LPABP is identical with liver fatty acid-binding protein (L-FABP). This protein binds LPA, and stimulates mitochondrial and microsomal glycerophosphate acyltransferase (GAT) and the export of LPA from both the organelles. The mitochondrially synthesized LPA exported by L-FABP can be converted to phosphatidic acid by microsomes. L-FABP also stimulates microsomal conversion of LPA to phosphatidic acid but strongly inhibits this reaction in mitochondria. However, in the absence of L-FABP mitochondria predominantly synthesize PA. Taken together, these findings are suggestive that L-FABP plays a major role in mitochondrial and microsomal phospholipid metabolism by regulating both the synthesis and utilization of LPA.
Vancura
A
A
Department of Biological Sciences, St. John's University, Jamaica, New York 11439.
Haldar
D
D
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D008970:Molecular Weight; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010712:Phosphatidic Acids / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008246:Lysophospholipids; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010712:Phosphatidic Acids; D010743:Phospholipids; D000217:Acyltransferases