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. The key role that the enzyme plays in triacylglycerol synthesis indicates it may be a potential drug target to ameliorate obesity in humans. The enzyme activity, which is critical to the growth and virulence of pathogenic fungi, is a proposed target for therapeutic development to ameliorate fungal infections.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jbior.2025.101074 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The compensatory enrichment of sphingosine-1-phosphate on HDL in FSGS enhances the protective function of glomerular endothelial cells compared to MCD.
Sci Rep
January 2025
Department of Nephrology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
Glomerular endothelial cells (GECs) are pivotal in developing glomerular sclerosis disorders. The advancement of focal segmental glomerulosclerosis (FSGS) is intimately tied to disruptions in lipid metabolism. Sphingosine-1-phosphate (S1P), a molecule transported by high-density lipoproteins (HDL), exhibits protective effects on vascular endothelial cells by upregulating phosphorylated endothelial nitric oxide synthase (p-eNOS) and enhancing nitric oxide (NO) production.
View Article and Find Full Text PDFInsights into phosphatidic acid phosphatase and its potential role as a therapeutic target.
Adv Biol Regul
January 2025
Department of Food Science and the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ, 08901, USA.
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 PDFBiomarkers.
Alzheimers Dement
December 2024
Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK.
Background: GRN mutations are a common cause of frontotemporal dementia (FTD), with previous studies linking granulin deficiency to reduced bis(monoacylglycerol)phosphate (BMP) levels, which ultimately impairs ganglioside degradation. BMP is involved in the lysosomal functions within cells, as it facilitates the adhesion of hydrolases and activator proteins where the lysosomal membranes meet, therefore a lack of BMP could impact lysosome function and integrity. We hypothesised that urine levels of BMP isoforms will be lower in FTD patients with GRN haploinsufficiency, as a reflection of reduced BMP in neural tissues, when compared to those with FTD caused by C9orf72 expansions and MAPT mutations, or healthy controls.
View Article and Find Full Text PDFDeveloping Topics.
Alzheimers Dement
December 2024
University of Illinois Urbana Champaign, Urbana Champaign, IL, USA.
Background: Increasing evidence shows that many lipids play important roles in the pathogenesis of Alzheimer's disease (AD), including Aβ plaque formation. Of note, the greatest genetic risk of late onset AD, apolipoprotien E4 (APOE4), plays a major role in lipid transport. However, the profile of lipids that play a role in AD is poorly understood.
View Article and Find Full Text PDFDiacylglycerol kinase δ is required for skeletal muscle development and regeneration.
FASEB Bioadv
January 2025
Department of Chemistry, Graduate School of Science Chiba University Chiba Japan.
Diacylglycerol kinase δ (DGKδ) phosphorylates diacylglycerol to produce phosphatidic acid. Previously, we demonstrated that down-regulation of DGKδ suppresses the myogenic differentiation of C2C12 myoblasts. However, the myogenic roles of DGKδ in vivo remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!