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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Lipids as Anchors01:32

Lipids as Anchors

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...

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Related Experiment Video

Updated: May 12, 2026

Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

Nutrient-dependent phosphorylation channels lipid synthesis to regulate PPARα.

Anne P L Jensen-Urstad1, Haowei Song, Irfan J Lodhi

  • 1Department of Medicine, Washington University School of Medicine , St. Louis, MO, USA.

Journal of Lipid Research
|April 16, 2013
PubMed
Summary

Fatty acid synthase (FAS) regulates liver metabolism by compartmentalizing its activity. Nutrient status dictates FAS phosphorylation, influencing its cytoplasmic activity and Peroxisome proliferator-activated receptor alpha (PPARα) target gene expression.

Keywords:
de novo lipogenesisperoxisome proliferator-activated receptor αstarvation

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Oligopeptide Competition Assay for Phosphorylation Site Determination
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Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Peroxisome proliferator-activated receptor (PPAR)α is a nuclear receptor crucial for coordinating liver metabolism, particularly during fasting.
  • Fatty acid synthase (FAS) plays a dual role in energy storage and activating hepatic PPARα through endogenous ligand synthesis.

Purpose of the Study:

  • To elucidate the paradoxical relationship between FAS and hepatic PPARα activation.
  • To investigate the role of subcellular compartmentalization and covalent modification of FAS in regulating liver metabolism and gene expression.

Main Methods:

  • Analysis of cytoplasmic versus membrane-associated FAS activity in mouse liver and hepatoma cells under varying nutritional conditions.
  • Site-directed mutagenesis of key phosphorylation sites on FAS (Thr-1029 and Thr-1033).
  • Pharmacological inhibition of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) using rapamycin and assessment of FAS activity and PPARα target gene expression.
  • Gene silencing of FAS to confirm its role in rapamycin-mediated effects.

Main Results:

  • Fasting increases the ratio of cytoplasmic to membrane FAS activity, indicating enhanced cytoplasmic FAS activity during PPARα activation.
  • Nutrient-dependent and compartment-selective phosphorylation of FAS at Thr-1029 and Thr-1033 occurs during feeding or insulin treatment.
  • Mutating these phosphorylation sites enhances PPARα target gene expression.
  • mTORC1 inhibition reduces FAS phosphorylation, boosts cytoplasmic FAS activity, and increases PPARα target gene expression, an effect dependent on FAS presence.

Conclusions:

  • Hepatic FAS activity is differentially regulated in cytoplasmic and membrane-associated compartments based on nutritional status.
  • Compartment-specific covalent modification of FAS, particularly phosphorylation, is a key mechanism linking nutrient availability to PPARα-mediated gene expression.
  • FAS acts as a crucial sensor, channeling lipid synthesis through distinct subcellular locations to modulate gene expression according to metabolic needs.