Phospholipid homeostasis in phosphatidylserine synthase-2-deficient mice.
Phosphatidylserine (PS) is synthesized in mammalian cells by two distinct serine-exchange enzymes, phosphatidylserine synthase-1 and -2. We recently demonstrated that mice lacking PS synthase-2 develop normally and exhibit no overt abnormalities [Bergo et al., (2002) J. Biol. Chem. 277:47701-47708]. We now show that PS synthase-2 mRNA levels are up to 80-fold higher in livers of embryos than in adults. Despite reduced serine-exchange activity in several tissues of PS synthase-2 deficient mice, the phospholipid composition of mitochondria and microsomes from these tissues is normal. Although PS synthase-2 is highly expressed in neurons, axon extension of cultured sympathetic neurons is not impaired by PS synthase-2 deficiency. We hypothesized that mice compensate for PS synthase-2 deficiency by modifying their phospholipid metabolism. Our data show that the rate of PS synthesis in hepatocytes is not reduced by PS synthase-2 deficiency but PS synthase-1 activity is increased. Moreover, PS degradation is decreased by PS synthase-2 deficiency, probably as a result of decreased PS degradation via phospholipases rather than decreased PS decarboxylation. These experiments underscore the idea that cellular phospholipid composition is tightly controlled and show that PS synthase-2-deficient hepatocytes modify phospholipid metabolism by several compensatory mechanisms to maintain phospholipid homeostasis.
Steenbergen
Rineke
R
Canadian Institutes for Health Research Group on the Molecular and Cell Biology of Lipids and Department of Medicine, University of Alberta, 328 HMRC, Edmonton, Alberta, Canada T6G 2S2.
Nanowski
Terry S
TS
Nelson
Randy
R
Young
Stephen G
SG
Vance
Jean E
JE
D000818:Animals; D005260:Female; D006706:Homeostasis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008861:Microsomes / Q000737:chemistry; D008928:Mitochondria / Q000737:chemistry; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D019884:Nitrogenous Group Transferases / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology; D014316:Tritium / Q000378:metabolism
D007527:Isoenzymes; D010743:Phospholipids; D012333:RNA, Messenger; D014316:Tritium; D012694:Serine; D019884:Nitrogenous Group Transferases; C111493:Ptdss2 protein, mouse