The phosphatidic acid or phosphatidate, It is a phospholipid belonging to the family of glycerophospholipids or phosphoglycerides, which are present in all biological membranes. It is the simplest phospholipid and functions as a precursor to other more complex glycerophospholipids, although it is not found in large quantities.
On E. coli, for example, it represents less than 0.5% of the total phospholipids in the plasma membrane and changes rapidly due to its role as a biosynthetic intermediate.
This precursor phospholipid is formed by the acylation of the hydroxyl groups of glycerol 3-phosphate with two activated fatty acid molecules and is believed to be present in virtually all biological membranes..
Cardiolipin, an important phospholipid present in the mitochondrial membrane and the plasma membrane of bacteria and archaea, is made up of two phosphatidic acid molecules attached to a glycerol molecule.
Lysophosphatidic acid, that is, a phosphatidic acid molecule lacking an acyl group, participates as an intermediate molecule in many extracellular signaling processes.
Article index
Like most phospholipids, phosphatidic acid is an amphipathic molecule with two ends of opposite hydrophilicity: a hydrophilic polar end and hydrophobic apolar tails..
As mentioned previously, this is the simplest phospholipid, since its "head" or polar group is composed only of the phosphate group that is attached to the carbon at position 3 of a glycerol molecule..
Their apolar tails are made up of two fatty acid chains esterified to the carbons at positions 1 and 2 of glycerol 3-phosphate. These fatty acids have varying lengths and degrees of saturation.
Usually, the length of the attached fatty acids ranges from 16 to 24 carbon atoms; and it has been determined that the fatty acid attached to carbon 2 is usually unsaturated (presence of carbon-carbon double bonds), although this depends on the organism considered, since in plant plastids it is a saturated fatty acid.
Phosphatidic acid biosynthesis is the branch point for the synthesis of the other glycerophospholipids. It begins with the activation of fatty acids by the addition of a CoA portion, a reaction catalyzed by acyl-CoA synthetase, which produces acyl-CoA.
There are different isoforms of this enzyme found in the endoplasmic reticulum and in the mitochondria, but the reactions occur in much the same way as in prokaryotes..
The first “committed” step of the biosynthetic pathway is the transfer of the acyl-CoA molecule to glycerol 3-phosphate, a reaction catalyzed by a glycerol 3-phosphate acyltransferase associated with the outer membrane of the mitochondria and with the reticulum. endoplasmic.
The product of this reaction, a lysophosphatidic acid (since it has only one hydrocarbon chain), is thought to be transferred from the mitochondria to the endoplasmic reticulum in order to carry out the second acylation reaction..
The enzyme that catalyzes this step is known as 1-acylglycerol 3-phosphate acyltransferase, abundant in the membrane of the endoplasmic reticulum and that specifically transfers unsaturated fatty acids to the carbon at position 2 of the 1-acylglycerol 3-phosphate molecule..
The phosphatidic acid thus formed can be hydrolyzed by phosphatidic acid phosphatase to 1,2-diacylglycerol, which can then be used for the synthesis of phosphatidylcholine and phosphatidylethanolamine..
An alternative pathway for the production of phosphatidic acid that involves the "recycling" of 1,2-diacylglycerol molecules has to do with the participation of specific kinase enzymes that transfer phosphate groups to the carbon in position 3 of diacylglycerol.
Another is from the hydrolysis of other phospholipids, catalyzed by enzymes known as phospholipases. An example of this process is the production of phosphatidic acid from phosphatidylcholine thanks to the action of phospholipase D, which hydrolyzes the bond between choline and the phosphate group of 1,2-diacylglycerol 3-phosphate.
Phosphatidic acid production in plants is associated with four different compartments of plant cells: plastids, endoplasmic reticulum, mitochondria, and the Golgi complex..
The first step of the route is the same as previously described, and in each compartment a glycerol 3-phosphate acyltransferase participates to transfer the activated acyl-CoA group to carbon 1 of a glycerol 3-phosphate molecule..
The synthesis is completed by an enzyme called lysophosphatidic acid acyltransferase after the transfer of another acyl group to the C3 position of lysophosphatidic acid..
In plastids of plants, this enzyme selectively transfers saturated fatty acids of a corresponding length with 16 carbon atoms. This is a particular attribute of the lipids synthesized in these organelles..
Phosphatidic acid is the precursor phospholipid for many phospholipids, galactolipids, and triglycerides in many organisms. Therefore, it is an essential molecule for cells, even though it does not fulfill direct structural functions..
In animals, one of the products of its enzymatic hydrolysis, 1,2-diacylglycerol, is used for the formation of triacylglycerides or triglycerides by transesterification with a third activated fatty acid molecule (associated with a CoA portion).
Triglycerides are important energy reserve molecules for animals, since the oxidation of the fatty acids present in them leads to the release of large amounts of energy and of precursors and intermediates in other metabolic pathways..
Another product of its hydrolysis, lysophosphatidic acid, is an important second messenger in some extracellular signaling pathways that involve its binding to receptors on the surface of other cells involved in tumorigenesis, angiogenesis, and immune responses, among others..
Its functions as a signaling molecule include its participation in the induction of cell proliferation, decreased apoptosis, platelet aggregation, smooth muscle contraction, chemotaxis, invasion of tumor cells, and others..
In bacteria, phosphatidic acid is necessary during a membrane phospholipid exchange process that provides the cell with “osmoprotective” molecules known as “membrane-derived oligosaccharides”..
Yet No Comments