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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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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...
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IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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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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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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Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

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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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Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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Updated: Jun 18, 2025

Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry

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Inositol Pyrophosphates as Versatile Metabolic Messengers.

Latika Nagpal1,2,3, Sining He4, Feng Rao4

  • 1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;

Annual Review of Biochemistry
|August 2, 2024
PubMed
Summary
This summary is machine-generated.

Inositol pyrophosphates are key signaling molecules regulating energy and metabolism. Studying their enzymes reveals crucial roles in maintaining mammalian metabolic homeostasis.

Keywords:
IP6KPPIP5Kenergy metabolisminositol hexakisphosphate kinaseinositol pyrophosphatesphosphate homeostasis

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Preparation of Quality Inositol Pyrophosphates
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Preparation of Quality Inositol Pyrophosphates

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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

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Last Updated: Jun 18, 2025

Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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Preparation of Quality Inositol Pyrophosphates
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

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Area of Science:

  • Cellular metabolism
  • Molecular signaling
  • Biochemistry

Background:

  • Inositol pyrophosphates (IPs) are evolutionarily conserved signaling metabolites.
  • Their roles as energy regulators, phosphodonors, and signaling messengers are increasingly recognized.
  • Enzymes metabolizing IPs are crucial for understanding their cellular functions.

Purpose of the Study:

  • To review the catalytic and regulatory mechanisms of inositol pyrophosphates kinases (IP6Ks) and diphosphoinositol pentakisphosphate kinases (PPIP5Ks).
  • To elucidate the functions of IPs in cellular and physiological processes.
  • To highlight evidence for IPs' role in mammalian metabolic homeostasis.

Main Methods:

  • Review of current literature on IP6Ks and PPIP5Ks.
  • Analysis of enzymatic pathways involving inositol pyrophosphates.
  • Examination of genetic and cellular evidence.

Main Results:

  • Inositol pyrophosphates, particularly 5-IP7 and IP8, are synthesized by IP6Ks and PPIP5Ks.
  • These molecules regulate phosphate homeostasis, ATP synthesis, insulin secretion, and energy utilization.
  • IPs are implicated as essential mediators of mammalian metabolic homeostasis.

Conclusions:

  • Inositol pyrophosphates play diverse and critical roles in cellular energy regulation and metabolic homeostasis.
  • Understanding the enzymes that synthesize and degrade IPs is key to deciphering their physiological significance.
  • Further research into IPs promises insights into metabolic diseases and therapeutic strategies.