Plasmalogens are unique lipid molecules that are critical to nerve, heart, lung and eye cells. They decrease dramatically with age and disease as the body can no longer produce enough.
Decades of research has shown that low plasmalogen levels are associated with brain and neurological diseases. Plasmalogen supplementation can help replenish these levels.
What are Plasmalogens?
Plasmalogens are a class of lipids that contain a vinyl ether (alkyl glycerophospholipid) at the sn-1 position and polyunsaturated fatty acids (PUFAs) at the sn-2 position. They are found in high concentrations throughout the body, including the brain, heart, kidneys, lungs, and eyes. They have antioxidant and signaling properties that help regulate cell function.
Plasmalogen synthesis is mediated by peroxisomal enzymes. The synthesis of plasmalogens is a complex reaction that involves the association of glyceronephosphate O-acyltransferase (GNPAT; also known as glyceronephosphate O-acyl-CoA acyltransferase) and alkylglycerone phosphate synthase on the luminal side of the peroxisomal membrane, followed by the generation of a fatty alcohol by fatty alcohol reductase 1 (FAR1).
The biosynthesis of choline and ethanolamine plasmalogens begins with the production of acetyl-D-glucose from DHA or eicosapentaenoic acid via acyl-D-glucose transferase. Next, the acyl-D-glucose is transferred to choline or ethanolamine through a glycerophospholipid transferase. After this, the phospholipid is hydrolyzed by choline or ethanolamine glycerophospholipid-specific phospholipase C or D.
This hydrolysis cleaves the fatty alcohol at the sn-1 chain to form a lysophospholipid with a highly reactive a-hydroxyaldehyde. This a-hydroxyaldehyde can then be oxidized by singlet oxygen, ROS, or hypochlorous acid, leading to the synthesis of a glycerol derivative with an acyl group attached to the sn-1 bond (Figure 1).
Defects in choline and ethanolamine plasmalogen synthesis are associated with rhizomelic chondrodysplasia punctata (RCDP) [85]. In addition, plasmalogen synthesis is required for the formation of the lipid rafts that line the membranes of certain cells.
Additionally, plasmalogens play an essential role in regulating the fluidity of membranes, lateral domain organization, and lipid-protein interactions. Low plasmalogen levels are associated with diseases like Alzheimer’s and Parkinson’s disease as well as virtually all cancers.
In humans, the most common plasmalogen defects are characterized by genetic disorders. These include RCDP and Zellweger spectrum, which is a syndrome involving a mutation in the PEX7 gene that controls peroxisomal localization of GNPAT and AGPS.
Plasmalogens are a class of essential lipids that are required for the maintenance of membranes and nerve cells. They are also critical for healthy aging, vascular health, and the prevention of disease. They are necessary for the proper development and maintenance of neurons, as well as cardiovascular, renal, pulmonary, and bone tissue. They are also important for the scavenging of free radicals.
Why are Plasmalogens important?
Plasmalogens are lipid molecules found in many cell membranes and play a crucial role in their function. They are important because they help maintain cellular membrane integrity, and they protect cells from oxidative stress by acting as sacrificial antioxidants. They also have a wide range of biophysical properties that impact the way proteins work, which is why they are so interesting to study.
One of the most notable differences between plasmalogens and other ether lipids is their vinyl-ether linkage at the sn-1 position, which prevents the formation of an ester bond. This enables them to have more lipophilicity than their diacyl phospholipid counterparts, which can lead to greater intermolecular hydrogen bonding between the head groups and changes in the arrangement of lipids within the membrane.
However, plasmalogens do not have the same ability to protect lipids from oxidative stress as diacyl phosphatidylcholines or phosphatidylethanolamines. They are more susceptible to oxidative stress because they have less energy than other polyunsaturated fatty acids and the vinyl-ether linkage is prone to being oxidized by various oxidizing reagents, including peroxyl radicals, metal ions, UV light, and singlet oxygen, as well as halogenating species like free aldehydes and hydroperoxides.
The synthesis of plasmalogens is regulated by glyceronephosphate O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS), which are present in the ER. Both enzymes can transfer acyl chains from the C16 and C18 fatty acids to the sn-1 oxidation position of glycerol and generate the lipids that make up plasmalogens.
Another key feature of plasmalogens is that their acyl chain can be rearranged, or hydroxylated, at the sn-2 position. This can lead to a change in the shape of the acyl chain, which in turn can alter the lateral packing of the lipid bilayer and the topological phase of the lipids within it. This has been shown to affect vesicle budding and virus envelope formation as well as the morphology of a plasma membrane’s liquid ordered domains.
These lipids are also a reservoir for signaling molecules, ion channels and other integral membrane proteins. In addition, they can act as an antioxidative agent by preventing the formation of free aldehydes and hydroperoxides from other unsaturated fatty acids, such as arachidonic acid, which have been linked to inflammation and other chronic diseases. Consequently, they are becoming increasingly important to human health.
How do Plasmalogens help my brain?
Plasmalogens are lipids found in high concentrations in the brain, heart, kidneys, lungs and eyes and are important for nerve cell function. They are also the most powerful antioxidants and free radical scavengers in our bodies.
They are a class of phospholipids that contain fatty alcohol at the sn-1 position and fatty acid at the sn-2 position on their glycerol backbone. They have a vinyl ether bond which allows them to react with oxygen to provide the antioxidant and neuroprotectant properties that are so vital for your brain health.
In addition to their importance for membrane and nerve function, plasmalogens are essential for the proper functioning of many other systems in the body, including organ development and tissue homeostasis. Deficiency in synthesis of these critical lipids can lead to peroxisomal diseases such as Zellweger’s syndrome, Rhizomelic Chondrodysplasia Punctata (RCDP) and secondary plasmalogen deficiency disorders such as Neimann-Pick type C.
These diseases can cause a significant decrease in the levels of plasmalogens in the blood and brain as well as reduced levels of brain DHA-plasmalogens, an essential component for healthy cognitive function. This decrease can lead to neurodegeneration and other problems.
Research shows that people with Alzheimer’s and Parkinson’s disease have lower plasmalogen levels than healthy individuals. Researchers believe that this decrease in plasmalogens could be a contributing factor to the symptoms and progression of these diseases.
Plasmalogens also help maintain healthy cell membranes by providing unique structural attributes that can protect them from oxidative damage, while facilitating signaling processes. They are enriched in DHA and AA, which provides them with additional anti-oxidative properties.
Moreover, they can also help in maintaining normal cell membrane fluidity, ion transport and the activity of membrane enzymes, receptor-mediated signaling, phagocytosis, synaptic transmission, and platelet activation. They are also a key source of bioactive signaling lipids such as DHA-choline.
There is a growing body of research suggesting that plasmalogen supplementation can help protect the brain by increasing its levels and helping preserve its neurons. Studies have shown that orally administered plasmalogen supplements can increase plasmalogen levels in tissue and blood serum tests by up to 40%.
Where can I get Plasmalogens?
Plasmalogens are phospholipids that are important to brain, heart, and other nerve cells. They are also found in the eyes, kidneys, and lungs and are depleted with age and disease.
Plasmalogen levels can decrease with aging and chronic stress, but can be replenished by taking a plasmalogen supplement. These supplements can help prevent and treat diseases that are caused by low plasmalogen levels, such as Alzheimer’s disease and Parkinson’s disease.
These supplements are also a great way to ensure your body has sufficient levels of plasmalogens, which are crucial for brain health. You can get these supplements by buying them online or from your doctor, who can prescribe the best type for you.
There are several natural sources of plasmalogens, such as fish oils and mollusks. However, these are difficult to extract and are only available in small quantities.
For instance, shark liver oil contains alkylglycerols (AG) that are enriched with plasmalogen precursors; chicken skin and scallops contain polyethyl-pls (PE-Pls), a major source of plasmalogens that is rich in antioxidants and essential fatty acids [71]. Other sources include oleuropein, an omega-3 fatty acid that is mainly found in seaweed.
Other lipid sources include arachidonic acid, another important omega-3 fatty acid that is also found in seaweed, and glycerol. Aside from their important roles in brain and nerve function, plasmalogens are also beneficial to the lipid membrane of the heart.
The biosynthesis of plasmalogens starts in the peroxisomes, which are the cells’ internal cellular waste-removing centers. In this part of the cell, plasmalogen precursors (including alkylglycerols and PE-Pls) are produced by a complex biochemical reaction called fatty acyl-CoA reductase 1 (Far1) that occurs on the external surface of the peroxisomal membrane.
Fatty acyl-CoA reductase is a rate-limiting enzyme that regulates the biosynthesis of plasmalogens. It is found in the cytoplasm of peroxisomes, and it is necessary for maintaining steady-state plasmalogen levels in the body.
Plasmalogens are also a powerful antioxidant and anti-inflammatory molecule. They are a critical component of the membranes of your heart, lungs, and eye cells and help to protect these tissues from free radical damage. They are also an essential building block for many other lipid molecules.