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What are Second Messengers?01:12

What are Second Messengers?

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Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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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...
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Amplifying Signals via Second Messengers01:15

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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
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Regulation of Metabolism01:19

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Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
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Calmodulin-dependent Signaling01:16

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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Related Experiment Video

Updated: Jun 19, 2025

Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators GECIs
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Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators GECIs

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Metabolic Messengers: itaconate.

A F McGettrick1, L A Bourner2, F C Dorsey2

  • 1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Nature Metabolism
|July 26, 2024
PubMed
Summary
This summary is machine-generated.

Itaconate is a key metabolite that regulates the immune system, impacting inflammation, obesity, and cancer. This review explores its diverse roles and therapeutic potential in immune and inflammatory diseases.

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Area of Science:

  • Immunology
  • Metabolism
  • Biochemistry

Background:

  • Itaconate is a crucial metabolite upregulated in inflammatory macrophages.
  • It is produced by the diversion of aconitate via aconitate decarboxylase 1, disrupting the tricarboxylic acid cycle.
  • Initial research focused on its anti-inflammatory roles, but its impact extends to other cell types.

Purpose of the Study:

  • To review itaconate's role as a key immunoregulatory metabolite.
  • To describe its diverse mechanisms of action and impact on immune and inflammatory responses.
  • To examine its clinical relevance and therapeutic potential in immune and inflammatory diseases and cancer.

Main Methods:

  • Literature review of immunological and metabolic studies on itaconate.
  • Analysis of itaconate's biochemical pathways and enzymatic production.
  • Examination of its effects across various cell types and disease models.

Main Results:

  • Itaconate exhibits significant immunoregulatory functions, including antibacterial defense and inflammation inhibition.
  • Emerging evidence highlights its inhibitory role in obesity.
  • Its impact on immune responses and cancer is increasingly recognized.

Conclusions:

  • Itaconate is a versatile immunometabolite with broad therapeutic potential.
  • Understanding its mechanisms is crucial for developing treatments for immune and inflammatory diseases.
  • Further research into itaconate's clinical applications is warranted.