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Regulation of phosphatidic acid phosphatase
Author(s) -
Carman George M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.408.3
Subject(s) - phosphatidic acid , diacylglycerol kinase , phosphatidylethanolamine , pld2 , biochemistry , dephosphorylation , lipid metabolism , biology , phospholipase d , microbiology and biotechnology , phospholipid , phosphatidylinositol , endocytosis , mutant , phosphatidylcholine , chemistry , phosphatase , gene , signal transduction , phosphorylation , cell , membrane , protein kinase c
Phosphatidic acid phosphatase (PAP) catalyzes the dephosphorylation of phosphatidic acid (PA) to yield diacylglycerol (DAG) and P i . The DAG generated in the reaction is used for the synthesis of triacylglycerol (TAG), and for the synthesis of phosphatidylethanolamine and phosphatidylcholine via the Kennedy pathway. By the nature of its reaction, PAP also controls the cellular content of PA, which is the precursor of phospholipids synthesized via the CDP‐DAG pathway. PA is also a signaling molecule that triggers phospholipid synthesis gene expression, membrane expansion, vesicular trafficking, secretion, and endocytosis. Biochemical and genetic studies to establish the roles of PAP in lipid metabolism became possible by the discoveries of the PAP‐encoding genes from the yeast Saccharomyces cerevisiae (e.g., PAH1 ) and mammals (e.g., LPIN1 ). The importance PAP in lipid metabolism is exemplified by its mutant phenotypes. In yeast, PAP mutants exhibit defects in the transcriptional regulation of phospholipid synthesis genes, the anomalous expansion of the nuclear/ER membrane, and a reduction in TAG content in stationary phase cells. Studies with mice and humans have shown that genetic defects in lipin 1 and lipin 2 are manifested in several metabolic diseases that include lipodystrophy, obesity, and peripheral neuropathy.