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Metabolic routing maintains the unique fatty acid composition of phosphoinositides.
Kim, Yeun Ju; Sengupta, Nivedita; Sohn, Mira; Mandal, Amrita; Pemberton, Joshua G; Choi, Uimook; Balla, Tamas.
Afiliación
  • Kim YJ; Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD, USA.
  • Sengupta N; Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD, USA.
  • Sohn M; Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD, USA.
  • Mandal A; Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD, USA.
  • Pemberton JG; Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD, USA.
  • Choi U; Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, NIAID, National Institutes of Health, Bethesda, MD, USA.
  • Balla T; Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, National Institutes of Health, Bethesda, MD, USA.
EMBO Rep ; 23(7): e54532, 2022 07 05.
Article en En | MEDLINE | ID: mdl-35712788
Phosphoinositide lipids (PPIn) are enriched in stearic- and arachidonic acids (38:4) but how this enrichment is established and maintained during phospholipase C (PLC) activation is unknown. Here we show that the metabolic fate of newly synthesized phosphatidic acid (PA), the lipid precursor of phosphatidylinositol (PI), is influenced by the fatty acyl-CoA used with preferential routing of the arachidonoyl-enriched species toward PI synthesis. Furthermore, during agonist stimulation the unsaturated forms of PI(4,5P)2 are replenished significantly faster than the more saturated ones, suggesting a favored recycling of the unsaturated forms of the PLC-generated hydrolytic products. Cytidine diphosphate diacylglycerol synthase 2 (CDS2) but not CDS1 was found to contribute to increased PI resynthesis during PLC activation. Lastly, while the lipid transfer protein, Nir2 is found to contribute to rapid PPIn resynthesis during PLC activation, the faster re-synthesis of the 38:4 species does not depend on Nir2. Therefore, the fatty acid side-chain composition of the lipid precursors used for PI synthesis is an important determinant of their metabolic fates, which also contributes to the maintenance of the unique fatty acid profile of PPIn lipids.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ácidos Fosfatidicos / Ácidos Grasos Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ácidos Fosfatidicos / Ácidos Grasos Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos