Publications by authors named "G P Carman"
Phosphatidic acid phosphatase, a conserved eukaryotic enzyme that catalyzes the Mg-dependent dephosphorylation of phosphatidic acid to produce diacylglycerol, has emerged as a vital regulator of lipid homeostasis. By controlling the balance of phosphatidic acid and diacylglycerol, the enzyme governs the use of the lipids for synthesis of the storage lipid triacylglycerol and the membrane phospholipids needed for cell growth. The mutational, biochemical, and cellular analyses of yeast phosphatidic acid phosphatase have provided insights into the structural determinants of enzyme function with the understanding of its regulation by phosphorylation and dephosphorylation.
View Article and Find Full Text PDFBiogenesis of membrane-bound organelles involves the synthesis, remodeling, and degradation of their constituent phospholipids. How these pathways regulate organelle size remains poorly understood. Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane.
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- Phosphatidic acid phosphatase (PAP) is an important enzyme involved in lipid metabolism, converting phosphatidic acid into diacylglycerol, which is vital for synthesizing fats and cell membranes.
- Researchers discovered that the antidepressant sertraline inhibits PAP activity in yeast and human cells, working through a noncompetitive mechanism and showing stronger inhibition than a common PAP inhibitor, propranolol.
- Molecular docking studies indicate that sertraline interacts with non-catalytic parts of the enzyme, and tests in yeast demonstrate that overexpressing PAP can counteract the inhibitory effects of sertraline on yeast growth and lipid content.
The Nem1-Spo7 phosphatase complex plays a key role in lipid metabolism as an activator of Pah1 phosphatidate phosphatase, which produces diacylglycerol for the synthesis of triacylglycerol and membrane phospholipids. For dephosphorylation of Pah1, the Nem1 catalytic subunit requires Spo7 for the recruitment of the protein substrate and interacts with the regulatory subunit through its conserved region (residues 251-446). In this work, we found that the Nem1 C-terminal region (CTR) (residues 414-436), which flanks the haloacid dehalogenase-like catalytic domain (residues 251-413), contains the conserved hydrophobic residues (L414, L415, L417, L418, L421, V430, L434, and L436) that are necessary for the complex formation with Spo7.
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- The synthesis and degradation of phospholipids are crucial for the biogenesis of membrane-bound organelles, specifically in regulating their size.
- A lipid degradation pathway was identified that inhibits the expansion of the endoplasmic reticulum (ER) membrane, which is influenced by certain enzymes known as phospholipid diacylglycerol acyltransferases (PDATs).
- The study focused on the yeast PDAT Lro1 and found that its activity can be altered, revealing that active Lro1 not only limits ER membrane expansion but is also regulated by diacylglycerol that affects its distribution and activity.