PHOSPHATIDYLSERINE: STRUCTURE, SYNTHESIS, FUNCTIONS, LOCATION - BIOLOGY - 2025

The phosphatidylserine is a lipid belonging to the family of the phospholipids and glycerolipids group or phosphoglycerides, derived from 1,2-diacyl glycerol 3-phosphate. Since it has an amino group in its structure, it is considered an amino phospholipid and is present in membranes of both eukaryotic and prokaryotic cells.

It was described for the first time by Folch, in 1941, as a secondary component of cephalin from the bovine brain (a cerebral lipid complex also made up of phosphatidylethanolamine) and, in 1952, Baer and Maurukas elucidated an important part of its chemical structure.

General scheme of phospholipids. (1) Hydrophilic head, (2) Hydrophobic tails, (A) Phosphatidylcholine, (B) Phosphatidylethanolamine, (C) Phosphatidylserine and (D) Scheme of a phosphatidylglycerol (Source: Foobar via Wikimedia Commons)

In eukaryotes, this phospholipid represents between 3 and 15% of membrane phospholipids and the variation in its abundance depends on the organism, the type of tissue, the type of cell in question and even the moment of its development..

Different studies have verified that it is absent in the mitochondria of eukaryotes, but its presence has been reported in the cell membranes of many bacteria, although the biosynthetic routes for its synthesis in these organisms are different.

The distribution of this phospholipid in cell membranes depends, in essence, on the enzymes that are responsible for its production and its movement (translocation) between the membrane monolayers depends on the action of amino phospholipid-flipases (in yeast) and scramblases. and translocases (in mammals).

It is an essential lipid for many cells of the nervous system, to such an extent that nutritional supplements have now been developed that include it in their formulations in order to improve certain brain capacities and prevent the degeneration of others.

Structure

Phosphatidylserine is a glycerophospholipid and as such is derived from a 1,2-diacyl glycerol 3-phosphate molecule, that is, from a glycerol molecule that has two esterified fatty acid chains on its carbons 1 and 2 and on carbon 3 has a phosphate group.

Structure of phosphatidylserine (Source: Zirgouflex via Wikimedia Commons)

Like all lipids, phosphatidylserine is an amphipathic molecule, with a hydrophilic polar end represented by the phosphate group and the serine that binds to it, and a hydrophobic apolar end, composed of fatty acid chains linked by ester bonds.

The name "phosphatidylserine" refers to all the possible combinations of fatty acids, of varying lengths and degrees of saturation, that are attached to a glycerol backbone that has a serine attached to the phosphate group on the polar head.

Synthesis

In prokaryotes

In prokaryotes, phosphatidylserine is produced by phosphatidylserine synthetases enzymes that associate with the plasma membrane or with ribosomal fractions, depending on whether it is Gram negative or Gram positive bacteria, respectively.

The synthesis of phosphatidylserine in these microorganisms is regulated and depends on the type and quantity of lipids available at the site where the synthetase enzyme is found.

In yeasts

Yeast phosphatidylserine synthetase synthesizes phosphatidylserine from the reaction between CDP-diacylglycerol and serine, generating phosphatidylserine and CMP. This phospholipid, in these organisms, is an important intermediate in the synthesis of phosphatidylcholine and phosphatidylethanolamine.

This reaction is regulated by intracellular concentrations of inositol, which has inhibitory effects on the enzyme. Other mechanisms involve the direct phosphorylation of the synthetase or some regulatory enzyme that is involved in the biosynthetic pathway.

In higher eukaryotes (plants and animals)

In organisms such as plants and animals (considered by some authors as higher eukaryotes) the synthesis of phosphatidylserine occurs through a calcium-dependent base exchange reaction through enzymes associated with the endoplasmic reticulum.

In this type of reaction, phospholipids are synthesized from pre-existing phospholipids, from which the polar group is removed and exchanged with a L-serine molecule.

In plants there are two phosphatidylserine synthetases: one that catalyzes the calcium-dependent base change reaction and the other that catalyzes in a reaction similar to that which occurs in yeast from CDP-diacylglycerol.

Mammals also possess two phosphatidylserine synthetases: one catalyzes the synthesis of phosphatidylserine by an exchange reaction between a phosphatidylethanolamine and a serine and the other does the same, but using a phosphatidylcholine as a base substrate.

Features

Phosphatidylserine is found in all types of eukaryotic cells; and in mammals it has been shown that, although it is not equally abundant in all tissues and it is not one of the phospholipids found in the highest proportion, it is essential for the survival of cells.

The fatty acid chains associated with phosphatidylserine molecules in the cells of the nervous system of many vertebrates play a fundamental role in the functioning of the nervous system.

On the cell surface

In addition to its structural functions for the establishment of biological membranes, the "redistribution" of phosphatidylserine marks the beginning of numerous physiological processes at the cellular level in mammals, so it could be said that it is involved in different cellular signaling processes.

Examples of these processes are blood coagulation, where phosphatidylserine is translocated towards the outer monolayer of the plasma membrane of platelets, which contributes to the accumulation of various coagulation factors towards the surface of these cells.

A similar process occurs during the maturation of sperm cells, but is seen more as a "dissipation" of the asymmetric distribution of this phospholipid (which enriches the inner surface of the plasma membrane).

The initial events of programmed cell death (apoptosis) are also characterized by the exposure of phosphatidylserine molecules to the cell surface, which "marks" apoptotic cells for digestion by phagocytic cells or macrophages.

Inside the cell

The intracellular functions of phosphatidylserine are closely related to its slightly cationic characteristics, since, through its charge, it can associate with various peripheral proteins that have negatively charged regions.

Among these proteins, some kinases and GTPases can be highlighted, which are activated once they associate with the phospholipid in question.

Phosphatidylserine participates in the "tagging" of some proteins to direct them towards phagosomes in recycling or degradation pathways and also in modifying the catalytic activity of others.

It has been shown that the formation of certain ion channels depends on the association of the proteins that constitute them with phosphatidylserine.

It is a source of precursors for the synthesis of other phospholipids, such as phosphatidylethanolamine, which can be formed from the decarboxylation of phosphatidylserine (phosphatidylserine is the precursor of mitochondrial phosphatidylethanolamine).

Where is it located?

Phosphatidylserine, like most phospholipids, is found in almost all cell membranes and enriches the cell membranes of nervous tissues; and, in the eye, it is particularly abundant on the retina.

In cells where it is found, to a greater or lesser extent, it is usually found in the inner monolayer of the plasma membrane and in endosomes, but it is rare in mitochondria.

As described in 1941, along with phosphatidylethanolamine, phosphatidylserine is part of a substance known as cephalin in the brain of many mammals.

Benefits of its intake

The importance of phosphatidylserine in the functioning of the nervous system has been studied extensively and for several decades it has been considered that its intake may be beneficial for the health of the central nervous system.

Several studies have concluded that the addition of phosphatidylserine in the diet as a nutritional supplement can have positive effects on improving memory, learning, concentration and mood declines related to age or aging.

It is thought to prevent loss of memory and other cognitive activities such as reasoning, abstract thinking, psychomotor impairment, changes in personality and behavior, and other important mental functions.

In some more specific studies on patients with memory problems, the intake of phosphatidylserine directly contributed to the learning of names and faces, the recall of names and faces and facial recognition.

A natural source of this phospholipid is fish. However, the species regularly included in nutritional supplements are obtained from the cerebral cortex of bovines or from soybeans.

Both types of phospholipids fulfill the same functions, but differ in the characteristics of the fatty acids of their apolar tails.

It has also been suggested that non-membrane-associated phosphatidylserine taken as a supplement (exogenous) may contribute to cellular defense against oxidative stress.

Contraindications

The first studies and clinical trials carried out with this phospholipid as a nutritional supplement revealed that its intramuscular administration can cause irritation and "burns", and that its intravenous administration has no known adverse effects.

By means of oral administration it appears to be a safe drug, but, in doses higher than 600 mg administered before bedtime, it can cause insomnia. However, reports indicate that it is safe and effective, especially if it is combined with a healthy lifestyle, which includes physical exercise and good nutrition.

Although a large number of studies have shown that the ingestion of this phospholipid does not produce harmful changes in blood biochemistry, one of the possible contraindications is related to the transfer of infectious diseases such as spongiform encephalopathy due to the consumption of brain extracts contaminated with prions.

References

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