plasmalogen

This image came from Med Life Discoveries. Med Life Discoveries has some interesting, lay friendly videos describing synaptic vesicle fusion and release neurotransmitters from the pre-synaptic neuron onto the post synaptic neuron. This relates to Alzheimer’s Disease and some of their endeavors. The featured image reiterates the basic structure of plasmalogens and head and acyl chain options discussed in this post.

Plasmologens from mussels[1]

This nice little study out of the Ocean University of China and other Chinese groups tested a neuronal like cell line with about 92% pure plasmolgens isolated from mussels. These plasmalogens included:

• phosphatidylethanolamine plasmalogens (50.13%)
• phosphatidylcholine plasmalogens (41.43%)
• The remaining 8% contained phospholipids phosphatidyl choline (outer leaflet and phosphatidyl ethanolamine (inner leaflet)
• Unsaturated fatty acids made up around 50% of the acyl groups of the phospholipids and he plasmalogens.
• Eicosapentaenoic acid was the major constituent of unsaturated fatty acids: 46% in Pls and 42% in phospholipids.

Eicosapentaenoic is considered an omega-3 fatty acid with 20 carbons and five double bonds. It is a precursor for prostaglandins, throboxanes, and leukotrienes. The SH-SY5Y human neuroblastoma cell line was used as a surrogate for neurons. While there is much dicussion of plasmologens being part of synaptic vesicle fusion in neurotransmitter release, Feng and coauthors were following up on the observation that plasmalogens (20 μg/mL in the medium)significantly decreased intracellular and extracellular levels of Aβ₄₂ in Chinese hamster ovary cells expressing the amyloid precursor protein in an Alzheimer’s Disease model. Surely these events required endocytosis and autophagy. As a general note, plasmalogens are also very abundant in myelin. Myelin is produced by glial cells that wrap themselves about neurones.

The authors had some impressive imagery of the cells that will not be presented in this post.

KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances

Rich factor is the ratio of numbers of differentially expressed genes annotated in this pathway term to the numbers of all genes annotated in this pathway term. For instance, of all of the endocytosis genes, a little over 7% are differentially expressed in response to the plasmalogen treatment. A little over 8% of the total autophagy genes are differentially expressed in reponse to plasmalogen from mussels.

• ADORA2A is the adenosine A2A receptor, the same receptor that is inhibited by caffeine.  It is interesting and cautionary that this particular mussel extract knocked the transcription of this gene down to almost nothing.
• APP, the amyloid beta precursor protein, something we’d like less of. 
• ATP6V1C2 is one of many lysosomal H⁺ pumps.
• Bcl2  regulates cell death by controlling the mitochondrial membrane permeability
• DGKK Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids
• GSAP Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intra membrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD
• GSK3  glycogen synthase kinaes subunit 3
• IL33 interleukin 33
• Slc18A2  Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports a variety of catecholamines such as dopamine, adrenaline and noradrenaline, histamine, and indolamines such as serotonin

moving on

This was a really nice study. This post is not doing justice for the deep dive into genomic analysis. The focus is on autophagy and lysosomes, so we have to contain things. The next question is which sources of meat have the best plasmalogens. As we re about to discover, land animals seem to be quite different.

Plasmalogen composition of common meats [2]

This particular study came out of Hokkaido University,in Japan. The goal was to have a plasmalogen profile of common meats from land and ocean animals. A combination of iquid chromatography and mass spectrometry were used to profile plasmalogens using these as standards

• PlsEtn-p16:0/18:1n-9,
• PlsEtn-p16:0/18:2n-6
• PlsEtn-p16:0/20:5n-3
• PlsCho-p16:0/18:1n-9
• PlsCho-p16:0/18:2n-6
• PlsCho-p16:0/20:5n-3
• PlsEtn-p16:0/17:0
• PlsCho-p16:0/17:0

PlsEtn has the ethanolamine head group and PlsCho the choline head group. p16 means the acyl chain at the SN1 carbon of glycerol has 16 carbons. n-9 refers to a double bond at the 3rd carbon of an 18 carbon acryl chain with just one double bond. The name of htis fatty acid is oleic acid.

The meats with more total plasmalogens…

This one might be a surprise to many readers…

A simple explanation given by the authors is that land animals have a lower water content in their tissues.

Ethanolamine vs choline as head groups…

Please consult the featured image for the structures of choline and ethanolamine. The phopolipid phsosphatidyl choline has a reputation for being the outer leaflet of the lipid bilayer.

Wu and coauthors briefly acknowledged the potential health benefits of supplementing with phospholipids with both head groups. This ambiguity is something for those who have considered supplementing with phosphatidyl choline/lecithin.

Acyl chain variability…

Wu and coauthors briefly discussed recommendations of the World Health Organization that the our diets contain less double bonds at the n=6 carbon. The featured image contains oleic acid with the double bond at the sixth carbon. Note that he kink is in the center of the acyl chain in this 3D rendering. Having the double bond kink in the center leads to in creased susceptibility to inflammation.

The authors acknowledged that all of the seafood came from the same area around Hokkaido area of Japan at the same time of year. There might be temperature and location variability. They also only used “edible” parts of the animals that may or may not have included organ meat and brains.

Brain plasmalogen studies from 1980s Russia

• Fish and frog brains, especially the myelin, contain higher amounts of the ethanolamine variety of plasmalogen [3] The acyl chains tend to be more unsaturated in cold blooded vertebrates.
• Another Russian language publication from this era compared plasmalogens in the brains of fish, frog, turtle, and pigeon. The plasmalogen content increased with the complexity of the nervous system. [4]
• A 1988 Russian study compared the plasmalogen content of brain fractions in four different species of birds. Myelin had the highest levels. The degree of unsaturation and PlsEtn was similar to brains of other cold and warm blooded animals. [5]

Fish heads might be a good source of dietary plasmalogens because they are sold in specialty Asian grocery stores in the US and the brains therein are not subjected to the same regulations of mammalian brains in the US, Canada, EU, and UK. The big question is whether fish heads could be a good source of dietary plasmalogens for those with any neurological condition in which autophagy is challenged. The scientific literature does not have that much to say about the matter, but the Med Life Discoveries work presented at the top of this post looks interesting.

References

1. Feng J, Song G, Shen Q, Chen X, Wang Q, Guo S, Zhang M. Protect Effects of Seafood-Derived Plasmalogens Against Amyloid-Beta (1-42) Induced Toxicity via Modulating the Transcripts Related to Endocytosis, Autophagy, Apoptosis, Neurotransmitter Release and Synaptic Transmission in SH-SY5Y Cells. Front Aging Neurosci. 2021 Nov 26;13:773713. PMC free article
2. Wu Y, Chen Z, Jia J, Chiba H, Hui SP. Quantitative and Comparative Investigation of Plasmalogen Species in Daily Foodstuffs. Foods. 2021 Jan 8;10(1):124. PMC free article
3. Kruglova EE. Sootnoshenie i sostav plazmalogennoĭ i diatsil’noĭ form fosfatidilétanolamina v subkletochnykh fraktsiiakh mozga foreli Salmo irideus i liagushki Rana temporaria [Correlation and composition of the plasmalogen and diacyl forms of phosphatidylethanolamine in subcellular brain fractions of the trout Salmo irideus and the frog Rana temporaria]. Zh Evol Biokhim Fiziol. 1986 Jan-Feb;22(1):30-6. Russian. PubMed
4. Kruglova EE. Raspredelenie plazmalogenov v subkletochnykh fraktsiiakh mozga pozvonochnykh [Plasmalogen distribution in the subcellular fractions of the vertebrate brain]. Zh Evol Biokhim Fiziol. 1985 Jul-Aug;21(4):411-4. Russian. PubMed
5. Kruglova EE. Sootnoshenie i sostav plazmalogennnoĭ i diatsil’noĭ form fosfolipidov v subkletochnykh fraktsiiakh mozga ptits [Ratio and composition of the plasmalogen and diacylated forms of phospholipids in subcellular fractions of the avian brain]. Zh Evol Biokhim Fiziol. 1988 Jan-Feb;24(1):21-7. Russian. PMC free article