Lipid signaling

Common lipid signaling molecules:<BR>lysophosphatidic acid (LPA)<BR> sphingosine-1-phosphate (S1P)<BR>platelet activating factor (PAF)<BR>anandamide or arachidonoyl ethanolamine (AEA)
Sphingolipid second messengers. Ceramide is at the metabolic hub, leading to the formation of other sphingolipids.
Cartoon of second messenger systems. Figure adapted From Barbraham Institute Mike Berridge. (accessed Jan. 21, 2008).

Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses.

- Lipid signaling

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Ceramides are a family of waxy lipid molecules.

Ceramide. R represents the alkyl portion of a fatty acid.
General structures of sphingolipids

Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.


Glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages.

PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation. Note: PLC is not an intermediate like the image may confuse, it actually catalyzes the IP3/DAG separation

In biochemical signaling, diacylglycerol functions as a second messenger signaling lipid, and is a product of the hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by the enzyme phospholipase C (PLC) (a membrane-bound enzyme) that, through the same reaction, produces inositol trisphosphate (IP3).


Macro biomolecule that is soluble in nonpolar solvents.

Structures of some common lipids. At the top are cholesterol and oleic acid. The middle structure is a triglyceride composed of oleoyl, stearoyl, and palmitoyl chains attached to a glycerol backbone. At the bottom is the common phospholipid phosphatidylcholine.
I2 - Prostacyclin (an example of a prostaglandin, an eicosanoid fatty acid)
LTB4 (an example of a leukotriene, an eicosanoid fatty acid)
Example of an unsaturated fat triglyceride (C55H98O6). Left part: glycerol; right part, from top to bottom: palmitic acid, oleic acid, alpha-linolenic acid.
Chemical structure of cholesterol.
Prenol lipid (2E-geraniol)
Structure of the saccharolipid Kdo2-lipid A. Glucosamine residues in blue, Kdo residues in red, acyl chains in black and phosphate groups in green.
Self-organization of phospholipids: a spherical liposome, a micelle, and a lipid bilayer.

The functions of lipids include storing energy, signaling, and acting as structural components of cell membranes.


18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid.

Sphingosine synthesis
General structures of sphingolipids

This leads to the formation of sphingosine-1-phosphate, a potent signaling lipid.


X, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides.

Biosynthesis of phosphatidylinositol catalyzed by phosphatidylinositol synthase. Figure adapted from Christopher, K.; van Holde, K.E.; Ahern, Kevin G. Biochemistry Third Edition. Pearson Education, Inc: Singapore, 2005; p 678.
Membrane lipids

Phosphorylated forms of phosphatidylinositol (PI) are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking.


Phytocannabinoid tetrahydrocannabinol (Delta-9-THC), the primary intoxicating compound in cannabis.

The bracts surrounding a cluster of Cannabis sativa flowers are coated with cannabinoid-laden trichomes
Cannabis indica plant
Anandamide, an endogenous ligand of CB1 and CB2

Endocannabinoids serve as intercellular 'lipid messengers', signaling molecules that are released from one cell and activating the cannabinoid receptors present on other nearby cells.

Lysophosphatidic acid

Production of LPA by Autotaxin

Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.


Endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor.

The bracts surrounding a cluster of Cannabis sativa flowers are coated with cannabinoid-laden trichomes

2-Arachidonoylglycerol is synthesized from arachidonic acid-containing diacylglycerol (DAG), which is derived from the increase of inositol phospholipid metabolism by the action of diacylglycerol lipase.

Sphingosine kinase

Conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine.

Sphingosine kinase 1, hexamer, Human
De novo synthesis

Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate, are lipid second messengers involved in diverse cellular processes.

Lysophospholipid receptor

The human beta-2 adrenergic receptor in complex with the partial inverse agonist carazolol.

The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling.