PC choline to stabilize membranes

LucH

Whatever the fat is [C16-0 (palmitic acid) or C18-n2 (LA, omega-6) or 18:3 n-3 (ALA, omega-3)], the PC will be hydrolyzed before reaching the destination. Need lipoprotein transport.
Excerpt:
Any dietary PC (egg yolk, soy lecithin, sunflower lecithin, krill oil, PC supplements) is broken down into LPC + a fatty acid in the intestine before absorption.
So even if you take PC, your body creates LPC during digestion.

What happens in the intestine when we get choline form food or a supplement?
Pancreatic phospholipase A2 hydrolyzes PC → lysophosphatidylcholine (LPC) + a free fatty acid.
LPC and free fatty acids are incorporated into mixed micelles with bile salts. These micelles facilitate absorption into enterocytes.
So we need effective bile to optimize things.
I take betaine HCL 1x/day, rather at the evening meal, since pH secretion is top between 11 – 14 o’clock (for proteins) (with ginger and pepsin). (1)
Using forms that enhance cellular uptake
We know choline from food or from supplement are going to be emulsioned. Thus there is a change in the absorption way, no mitochondrial delivery, at the moment. Whatever the form is.
PS: I've tried to understand how the metabolism manage to assimilate PC choline. => 9 pages to summarize "How PC Is Digested, Emulsified, Transported, and Ultimately Reaches Mitochondria".
Livre science-fiction.png

bio3nergetic

@alfredoolivas The knockout LPCAT3 mice have reduced PUFA content in PC AND are protected from diet-induced fatty liver. The correlated fatty liver disease from high fat/high PUFA diet, as it increased (unsaturated) PC, was lacking in these mice. This is rather straight forward in understanding. A mainstreamer perhaps would miss the connection as they don't think of the PUFA component.

Well for starters, from that study there are links to harder evidence for LPCAT3 PUFA preference. Others include:
Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
Tomomi Hashidate-Yoshida
PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
Liver X receptor agonist upregulates LPCAT3 in human aortic endothelial cells
Delphine Bousquet,
PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
Scott M. Johnson

The PC process is one of incorporation: you incorporate the lipids you ingest. The studies that show benefit from soybean oil PC have to do with contextual facts i.e. no PC is worse than some PUFA PC.

LPCAT3-driven PUFA-PC synthesis in high-fat, high-PUFA diets promotes fatty liver by fueling lipogenesis and VLDL overproduction.
Dietary soybean PC, however, acts as a hepatoprotective agent by improving lipid export, reducing inflammation, and supporting membrane health BUT likely because it bypasses uncontrolled remodeling.

Extra exogenous PC is better than nothing at all in the face of high fat diet. Exogenous PC (especially PUFA-PC like soybean or polyenylphosphatidylcholine/PPC) acts as a functional "rescue" molecule in high-fat diets, even if not ideal. However saturated PC is more stable and less prone to oxidation, making it potentially safer in the context of metabolic stress. Deciphering these studies often takes understanding the context or situation the lab animal is in.

alfredoolivas

@bio3nergetic I am not reffering to how prone saturated PC is to oxidation - I am referring to how pancreatic phospholipase A2 and stomach acid a pH of 1 would break PC bonds. There hasn't been a study on saturated PC in humans, but for other PC (polyethylene Pc)

"this suggests that most oral PC was hydrolyzed to lysolecithin before absorption.”
https://pubmed.ncbi.nlm.nih.gov/7175371/

"PC digestion occurs in the small intestine… Chemical breakdown of PLs is carried out primarily by pancreatic phospholipase A₂ (PLA₂) … It interacts with PLs at the sn-2 position to yield free fatty acid and lysoPC.”
https://pmc.ncbi.nlm.nih.gov/articles/PMC3257636/

bio3nergetic

@alfredoolivas said in PC choline to stabilize membranes:

"PC digestion occurs in the small intestine… Chemical breakdown of PLs is carried out primarily by pancreatic phospholipase A₂ (PLA₂) … It interacts with PLs at the sn-2 position to yield free fatty acid and lysoPC.”

Pancreatic phospholipase A2 and stomach acid a pH of 1 breaking PC bonds does not at all mitigate risk or toxicity of oxidation products, bioactivity of lysoPC, and systemic inflammatory potential of dietary oxidized lipids regarding PUFA. You are conflating these inherent processes with the idea that somehow the physiology is safe from the usual culprit.

LucH

Talk with AI
Context:
Title: PC choline to stabilize membranes.
I put in excerpt:
You aren’t talking the same language:

- One is speaking about altered PUFA as carrier (fueling lipogenesis and VLDL overproduction, upregulating LPCAT3 in human aortic endothelial cells), making saturated PC more stable and less prone to oxidation. The added PUFA (in the supplement) is problematic due to the LPCAT3 preference.
- The other one excerpting that most oral PC has been hydrolyzed to lysolecithin before absorption / incorporate in tissues (breakdown of PLs is carried out primarily by pancreatic phospholipase A₂.
  https://bioenergetic.forum/topic/9164/pc-choline-to-stabilize-membranes/8?_=1770916434026

My comment (LucH):
Whatever the fat is [C16-0 (palmitic acid) or C18-n2 (LA, omega-6) or 18:3 n-3 (ALA, omega-3)], the PC will be hydrolyzed before reaching the destination. Need lipoprotein transport.
Excerpt:
Any dietary PC (egg yolk, soy lecithin, sunflower lecithin, krill oil, PC supplements) is broken down into LPC + a fatty acid in the intestine before absorption.
So even if you take PC, your body creates LPC during digestion.

*) Request to AI
A comment to set things clear, though they don’t seem to speak the same language, trying to argue sth different.
Analyze, please, with an advice to set the eyes again in front of the holes!

Answer from AI (gemini3)
It looks like you've stepped into a classic "forest for the trees" debate. Both sides are technically correct about specific mechanisms, but they are arguing from different stages of the metabolic pipeline.
To "set the eyes back in front of the holes," we need to look at the transition from ingestion to integration. Here is a breakdown of the two positions and the reality of the biochemistry.

The Disconnect: Mechanism vs. Metabolism
The two sides are talking past each other because one is focused on downstream signaling (what the molecule does once it's in the cell) and the other is focused on upstream processing (what happens in the gut).
The Digestive Reality (The "Hydrolysis" Filter)
Your comment (LucH) hits the nail on the head regarding the "gatekeeper." When you ingest Phosphatidylcholine (PC), it doesn't travel through your blood like a whole Lego set.
 The Breakdown: Pancreatic phospholipase A₂ cleaves the fatty acid at the sn−2 position.
 The Result: You are left with Lysolecithin (LPC) and a Free Fatty Acid (FFA).
 The Absorption: These components are absorbed into the enterocytes (intestinal cells).
 The Re-assembly: Inside the enterocyte, they are often re-esterified into new phospholipids or triglycerides to be packed into chylomicrons.
The Bottom Line: You cannot "target" a specific membrane with a specific oral PC molecule because the body deconstructs it and puts it into the general fatty acid pool or re-assembles it based on current metabolic needs.
Where Side A Has a Point (The LPCAT3 Factor)
While Side B is right about the breakdown, Side A is right about the preference. Even if the PC is broken down into LPC, the enzyme LPCAT3 is the "re-builder."
LPCAT3 has a high affinity for polyunsaturated fatty acids (PUFAs). So, if your diet (or supplement) is flooded with PUFAs, LPCAT3 will preferentially grab those to rebuild the membrane. This is where the "fueling lipogenesis" and "VLDL overproduction" concerns come in. It’s not that the PC stayed intact; it’s that the raw materials provided by the supplement gave LPCAT3 the tools to build the "wrong" kind of membrane.

Advice to Re-Center the Debate
To clear the air, the conversation needs to move away from "What does this supplement molecule do?" to "What does this supplement do to the Intracellular Pool?"
The "Eyes in Front of the Holes" Perspective: Stop arguing about whether the PC stays intact (it doesn't). Start focusing on the ratio of fatty acids being introduced. If you flood the system with a PUFA-based PC supplement, you are providing the specific substrate that LPCAT3 uses to drive the exact metabolic pathways Side A is worried about.
The takeaway: The specific fatty acid "tail" on your PC supplement matters not because it survives digestion, but because it dictates the "parts list" available to your cells for reconstruction.
Would you like me to draft a concise "rebuttal" or summary you can post back to that forum thread to bridge these two points?
LucH says:
No need. Fine so. Just find a bullet end image. Analogy if pertinent. Material brought to VLD particles.
AI says
Think of the liver as a factory floor. The oral PC supplement isn't a "finished machine" arriving at the loading dock; it is a delivery of raw scrap metal.
 The Gut (The Shredder): Digestion is the shredder that breaks the PC into individual components (LPC and Fatty Acids).
 The Cell (The Assembly Line): Inside the cell, enzymes like LPCAT3 are the workers on the line. They don't care where the scrap came from; they just grab what is closest to them.
 The VLDL (The Shipping Crate): If you deliver a pile of PUFA-heavy scrap, the workers (LPCAT3) will build PUFA-rich membranes and pack them into the VLDL shipping crates.
The Point: If the parts you supplied are "oxidizable" or "pro-lipogenic" (PUFAs), it doesn't matter how expensive the original "Ferrari" was. Your body is now built out of those specific parts.
Bottom Line: Stop looking at the "PC" label on the bottle and start looking at the Fatty Acid profile on the back. That is the only material that actually makes it into the VLDL shipping crate.
Would you like me to generate an image of this "Biological Assembly Line" packing those VLDL crates?
LucH says:
Yes, but only with a two-side direction lines (==>). PNG.
PC choline. PUFA vehicle problem.png
The specific fatty acid "tail" on your PC supplement matters not because it survives digestion, but because it dictates the message available to your cells for reconstruction. Raw material available at the end will serve as a cargo. It’s not about the form the fat takes at the start; it’s about the raw material available at the finish line.
LucH says :
End. Thanks.
AI says:
It sounds like you've got a solid handle on the "cargo vs. vehicle" distinction now—the perfect way to bridge that gap in the forum debate.

alfredoolivas

@bio3nergetic said in PC choline to stabilize membranes:

and systemic inflammatory potential of dietary oxidized lipids regarding PUFA.

0.65g of soy / sunflower fatty acids in a gram of PC? I wouldn't worry about that at all.

bio3nergetic

@alfredoolivas Right, and as the understanding now settles into a different argument i.e. amount, it simply makes no sense to add in more PUFA regardless of amount when addressing PC exogenously. Where I allow my daily PUFA comes from whole food, eggs, etc. IF I consider exogenous use I'd look at something like mitolipin..

alfredoolivas

@bio3nergetic Every single study apart from two in vitro studies on the thread of Mitolipin, that showed it's beneficial effects were done using unsaturated phosphatidyl choline.

It's the end result that matters, not the theoretical effects of less than 1g of PUFA. To me.

Topical Administration:
The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model active ingredient. - PubMed - NCBI
The hypocholesterolemic and antiatherogenic effects of topically applied phosphatidylcholine in rabbits with heritable hypercholesterolemia. - PubMed - NCBI
Effects of phosphatidylcholine on the topical bioavailability of corticosteroids assessed by the human skin blanching assay. - PubMed - NCBI

General/Miscellaneous:
Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. - PubMed - NCBI
Biochemical effects of phosphatidylcholine treatment in rats. - PubMed - NCBI
Rapid stopping of A23187 action by phosphatidylcholine. - PubMed - NCBI
Blockade of alpha-adrenergic receptors by analogues of phosphatidylcholine. - PubMed - NCBI
The effect of mixed phosphatidylcholine liposomes on beef heart cytochrome c oxidase [proceedings]. - PubMed - NCBI
Cytochrome c Interaction with Cardiolipin/Phosphatidylcholine Model Membranes: Effect of Cardiolipin Protonation - ScienceDirect
Inhibition of mammalian cytotoxic cells by phosphatidylcholine and its analogue
Studies on cytochrome oxidase. Interactions of the cytochrome oxidase protein with phospholipids and cytochrome c. - PubMed - NCBI

Inflammation:
Anti-inflammatory action of a phosphatidylcholine, phosphatidylethanolamine and N-acylphosphatidylethanolamine-enriched diet in carrageenan-induced... - PubMed - NCBI
Anti-inflammatory effects of phosphatidylcholine. - PubMed - NCBI
Protective effect of phosphatidylcholine on lipopolysaccharide-induced acute inflammation in multiple organ injury. - PubMed - NCBI
Soy phosphatidylcholine inhibited TLR4-mediated MCP-1 expression in vascular cells. - PubMed - NCBI

Brain/Memory/Mood/Cognition/Nervous system:
Protective effects of phosphatidylcholine on oxaliplatin-induced neuropathy in rats. - PubMed - NCBI
Dietary phosphatidylcholine improves maze-learning performance in adult mice. - PubMed - NCBI
Impairment of brain mitochondrial functions by β-hemolytic Group B Streptococcus. Effect of cardiolipin and phosphatidylcholine. - PubMed - NCBI
Protective effects of a phosphatidylcholine-enriched diet in lipopolysaccharide-induced experimental neuroinflammation in the rat. - PubMed - NCBI
Effect of phosphatidylcholine on explicit memory. - PubMed - NCBI
A report on phosphatidylcholine therapy in a Down syndrome child. - PubMed - NCBI
http://www.amsciepub.com/doi/abs/10.2466/pr0.1986.58.1.207?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed&
http://www.sciencedirect.com/science/article/pii/S0140673683921086
[Combination of phosphatidylcholine and pentoxifylline in the therapy of progressive obstructive stroke]. - PubMed - NCBI

Liver/Gallbladder:
Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in vivo experiments. - PubMed - NCBI
Accumulation of lipid in rat liver was induced by vitamin B₆ deficiency and was ameliorated by supplemental phosphatidylcholine in the diet. - PubMed - NCBI
Hepatoprotective effect of phosphatidylcholine against carbon tetrachloride liver damage in mice. - PubMed - NCBI
Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholin... - PubMed - NCBI
[Effects of phosphatidylcholine pretreatment during acute experimental biliary reflux]. - PubMed - NCBI
Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid. - PubMed - NCBI
Phosphatidylcholine-enriched diet prevents gallstone formation in mice susceptible to cholelithiasis. - PubMed - NCBI
http://www.ncbi.nlm.nih.gov/pubmed/7539565
http://www.ncbi.nlm.nih.gov/pubmed/24292666
http://www.ncbi.nlm.nih.gov/pubmed/21745592
http://www.ncbi.nlm.nih.gov/pubmed/20832797
http://www.ncbi.nlm.nih.gov/pubmed/8276192
http://www.ncbi.nlm.nih.gov/pubmed/8276177

Heart/Kidney:
http://www.ncbi.nlm.nih.gov/pubmed/23684996
http://www.ncbi.nlm.nih.gov/pubmed/1420493

Cancer:
http://www.ncbi.nlm.nih.gov/pubmed/17399847
http://www.ncbi.nlm.nih.gov/pubmed/24772432
http://www.ncbi.nlm.nih.gov/pubmed/19579625

Obesity/Diabetes/Metabolism:
http://www.ncbi.nlm.nih.gov/pubmed/25445436
http://www.ncbi.nlm.nih.gov/pubmed/22468042
http://www.ncbi.nlm.nih.gov/pubmed/22145579
http://www.ncbi.nlm.nih.gov/pubmed/21614002

Bones:
http://www.ncbi.nlm.nih.gov/pubmed/19766625
http://www.ncbi.nlm.nih.gov/pubmed/19296835

Anti-viral/anti-bacterial:
http://www.ncbi.nlm.nih.gov/pubmed/9708184
http://www.ncbi.nlm.nih.gov/pubmed/8516563
http://www.ncbi.nlm.nih.gov/pubmed/1570416
http://www.ncbi.nlm.nih.gov/pubmed/1530351

bio3nergetic

@alfredoolivas For myself, and PUFA sensitivity as well as past IBD experience, it is not theoretical it is practical. My exception of PC , again is primarily through food first. That is my threshold of tolerance. Outside of that I have no interest in adding more PUFA. There is no reasonable or convincing argument to do otherwise if one's diet is sorted. The understanding of PC and its benefits are again, as a necessarily evil not as a point of putting PUFA on a pedestal. The effects mentioned have been demonstrated without the PUFA risk with saturated lipids. The understanding that far is sufficient to deduce that IF one is to use PC exogenously opt for saturated. If you don't want to for personal reasons, by all means go ahead.

LucH

Choline pathway explained
PC choline is hydrolyzed when metabolized (digestion).
2 situations:
Ratio is fine: PC → LPC → ## ↓ PLA₂ activation → ↓ free AA → ↓ PGE₂, when PL plays as a buffer (stabilizing the membranes). PLA2 acts as a "double-edged sword" (phagocytosis & downregulation of oxidative stress after ischemia).
Ratio is bad: PC → LPC → ## ↑ PLA₂ activation → ↑ free AA → ↑ Prostaglandins (PGE) and leukotrienes (Lts), when integrity is impaired.

Degradation of membrane PC activates the AA cascade, leading to pain and inflammatory responses (e.g., neuropathic pain). PC helps maintain ideal membrane fluidity ("homeoviscous adaptation") in the face of stress.
Neuronal protection: In neurons, AA-PC is concentrated along the axon, and its integrity is associated with actin dynamics and tactile sensitivity. The CDP-choline pathway is the main pathway for synthesizing PC necessary for membrane stabilization. Said on another way, citi-choline (or CDP-choline, it’s the same molecule) is required to go through the BBB.
Abbreviations:
AA = Arachidonic Acid
PLA2 = Phospholipase A2 (enzyme that cleaves membrane phospholipids, remodeling when required, used in host defense and signal transduction. Critical regulator).
PC = phosphatidylcholine
LPC = lysophosphatidylcholine
PE = phosphatidylethanolamine
PS = phosphatidylserine

Key Aspects of the Anti-Inflammatory Action
Mechanisms: The diet reduces the inflammatory leukocyte reaction. It also suppresses pro-inflammatory enzymes, such as those responsible for reactive oxygen species (ROS) production, and inhibits TNF-induced activation of the NF-B pathway.

Phospholipid Roles:
o PC: Known to stabilize cell membranes, modulate T-cell function, and reduce pro-inflammatory signaling in intestinal epithelial cells.
o PE: Regulates mitochondrial function in macrophages and aids in anti-inflammatory responses.
o NAPE (N-acylphosphatidylethanolamine): Linked to endocannabinoid metabolism, contributing to reduced inflammatory activation.
• Therapeutic Potential: Studies suggest that this combination (often studied with 1% PC, 0.4% PE, and 0.1% NAPE) can act as a novel, non-toxic, nutritional approach to managing chronic inflammatory conditions.
The combination of these phospholipids helps modulate the inflammatory cascade, suggesting they are potential agents for reducing systemic inflammation.

What happens in the intestine?
 Pancreatic phospholipase A2 hydrolyzes PC → lysophosphatidylcholine (LPC) + a free fatty acid.
 LPC and free fatty acids are incorporated into mixed micelles with bile salts.
These micelles facilitate absorption into enterocytes.
 LPC is re-acylated to PC using available fatty acids, then incorporated into chylomicrons and released into lymph → blood.
Key point
There is no direct route from dietary PC → mitochondria. Instead, PC enters systemic pools and participates in membrane turnover.
Mitochondria do not import PC efficiently from the cytosol. Instead, mitochondrial PC is mostly supplied by:
 Phosphatidylserine (PS) import → decarboxylation → PE → methylation → PC
 Contact sites between ER and mitochondria (MAMs)
PC is essential for mitochondrial membrane structure and protein translocases.
Important insight
Dietary PC does not directly enrich mitochondrial PC. Instead, it contributes to the general cellular PC pool, which indirectly supports mitochondrial membrane homeostasis.
Mitochondrial PC depends on intracellular lipid trafficking, not diet.
Mitochondria rely on:
• ER–mitochondria contact sites (ER = endoplasmic reticulum). ER forms a tubule / sac, for direct and functional contact with mitochondria for lipid and calcium signaling.
• Lipid transfer proteins (bridge organelles to allow transfer in aqueous spaces, like with PS or PE.
• Internal synthesis pathways
These mechanisms are rate limiting, not the dietary form of PC. (This statement implies that the rate-limiting step for maintaining mitochondrial phosphatidylcholine (PC) levels is the internal production and transport of phospholipids, rather than the amount of PC ingested in the diet).
Final Practical Takeaway
If you take PC → your body makes LPC.
If you take Alpha GPC → you get GPC directly.
• PC supplements give you the raw material for membranes, but they’re digested into LPC first.
• LPC is not taken as a supplement; your body makes it from PC.
• GPC (Alpha GPC) is a purified choline fragment of PC and is the easiest to supplement directly.
• Citicoline (CDP choline) → best for brain choline, not relevant to LPC (bypass way, direct incorporation))
🧬 The Link Between PC/LPC/GPC and Cardiolipin
Cardiolipin (CL) is the signature phospholipid of mitochondria, essential for:
• cristae structure (high-curvature structure to receive PC on an easier way, forming a highly organized structure to optimize the exchanges).
• electron transport chain stability
• cytochrome c anchoring
• ATP production
But cardiolipin is not made from PC, LPC, or GPC. Instead, the connection is indirect. The environment shapes CL and PC controls the membrane environment where cardiolipin is remodeled. So PC status indirectly determines cardiolipin quality.
The Real, Practical Connection
PC, LPC, and GPC do not become cardiolipin — they maintain the phospholipid environment that allows cardiolipin to be synthesized and remodeled correctly.

PC = the membrane “scaffold” that allows PE and CL to be handled correctly.
PE shapes the inner membrane so cardiolipin can function (appropriate curvature).
PC and PE balance controls cardiolipin remodeling (tafazzin activity). The PC : PE ratio is a master regulator of cardiolipin quality.
The Real, Practical Link
PC stabilizes the outer membrane, PE shapes the inner membrane, and cardiolipin organizes the respiratory machinery — all three lipids depend on each other to maintain mitochondrial cristae and ATP production.

Sources and references

Axonal Gradient of Arachidonic Acid-containing Phosphatidylcholine and Its Dependence on Actin Dynamics. doi: 10.1074/jbc.M111.316877 J Biol Chem. 2011
Arachidonic acid and lysophosphatidylcholine inhibit multiple late steps of regulated exocytosis.
https://doi.org/10.1016/j.bbrc.2019.05.106 2019 SciDir
Phosphatidylcholine is the major phospholipid providing arachidonic acid for prostacyclin synthesis in thrombin-stimulated human endothelial cells.
https://doi.org/10.1016/0049-3848(84)90068-9 2024 Sci Dir
Video 2.42’’ 2025: What is phosphatidylcholine? – The importance of PC. BOC Sciences
Youtube Video
The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. https://doi.org/10.1016/j.bbamem.2017.04.006
Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids in all mammalian cell membranes.
In recent years, the importance of phospholipid metabolism in regulating lipid, lipoprotein and whole-body energy metabolism has been demonstrated in numerous dietary studies and knockout animal models. The purpose of this review is to highlight the unappreciated impact of phospholipid.
Abnormally high and low cellular PC/PE ratios influence energy metabolism and is linked to disease progression.
Synopsis of arachidonic acid metabolism: A review
doi: 10.1016/j.jare.2018.03.005 J Adv Res. 2018
Under stress conditions (e.g., oxidative stress, injury), the Arachidonic Acid (AA) cascade is initiated via the PLA₂ pathway to produce pro-inflammatory mediators.

The Cascade Process:

Stimulus: Cellular stress (oxidative, inflammatory) activates Phospholipase A₂ (PLA₂).
Release: Activated PLA₂ hydrolyzes phospholipids in the cell membrane to release free Arachidonic Acid.
Metabolism: Free AA is converted by enzymes into bioactive lipids:

COX Pathway: Cyclooxygenase (COX-1/COX-2) converts AA into prostaglandins and thromboxanes.
LOX Pathway: Lipoxygenase (LOX) converts AA into leukotrienes.

Result: Generation of pro-inflammatory mediators that cause inflammation and promote disease progression.
This pathway is a major contributor to inflammation, neurodegenerative diseases (like ALS), and cardiovascular conditions.

Neuropathic pain
Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury.
doi: 10.1371/journal.pone.0177595 PlosOne 2017 May 24.
Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics.

To be continued on next post.

LucH

How to support PE production naturally (without supplements).
PE (phosphatidylethanolamine) is made mainly inside mitochondria by the enzyme PSD (phosphatidylserine decarboxylase):
Phosphatidylserine (PS) → PE
So the only way to increase PE naturally is to support:

PS availability
Mitochondrial PSD activity
ER–mitochondria lipid exchange
Membrane conditions that favor PE retention
Support PE Retention in Mitochondria
Even if you make PE, it can be lost if membranes are unstable.
Support naturally by:
• Adequate cholesterol (membrane stabilizer)
• Adequate saturated fats (reduce leakage)
• Avoiding PUFA overload (prevents peroxidation and PE loss)
Why this matters: PE is the lipid that gives curvature to cristae. If PE is low, cardiolipin cannot organize respiratory complexes.

Practical Summary
To support PE production naturally:

Eat enough serine + glycine
Eggs, dairy, meat, gelatin.
Maintain a healthy PC pool
Eggs, lecithin foods, or PC supplements if desired.
Support mitochondrial function
Stable blood sugar, move, low oxidative stress.
Support membrane stability
Saturated + monounsaturated fats, low omega 6.
Protect ER–mitochondria contact sites
Avoid alcohol excess, avoid PUFA overload.

Why this matters for cardiolipin
• PE shapes the inner membrane → cardiolipin can anchor ETC complexes.
• PC stabilizes the outer membrane → lipid traffic works.
• Cardiolipin organizes the respiratory chain → ATP production is efficient.
Supporting PE naturally = supporting cardiolipin function without adding PUFA.
To be continued on next post.

LucH

I'm going to end up with useful nutrients to protect lipid directly
1. Antioxidants That Protect Lipids Directly
Vitamin E (tocopherols + tocotrienols)
• Acts as the primary lipid-phase antioxidant, protecting membrane phospholipids from peroxidation.
• Gamma-tocotrienols add stronger chain-breaking antioxidant activity in membranes. Dose: 400 IU mixed tocopherols (with gamma tocotrienols) 2–3×/week, or 20–25 mg/day. Note: More is not better; excess can disrupt redox balance.
Beta-carotene (from food)
• Quenches singlet oxygen and supports antioxidant recycling.
• Best obtained from diet (carrots, sweet potatoes, leafy greens).
Astaxanthin
• A potent carotenoid that embeds across the lipid bilayer and protects both sides of the membrane from ROS.
• Particularly effective in mitochondrial membranes.

2. Water-Soluble Antioxidants and Cofactors
Vitamin C
• Regenerates oxidized vitamin E.
• Supports collagen, immune function, and general redox balance.
Magnesium
• Key mechanism: Magnesium inhibits PLA₂, the enzyme that releases arachidonic acid (AA) from membrane phospholipids.
• Mg²⁺ stabilizes phospholipid bilayers, reduces Ca²⁺-dependent PLA₂ activation, and lowers eicosanoid production. Dose: 350–420 mg/day elemental magnesium. Form: Magnesium bisglycinate (≈2.5 g/day split into 2–3 doses to reach ~450 mg). Note: Higher needs after stress; do not “preload” before stress.
Zinc
• Protects thiol groups and stabilizes membrane proteins.
• Inhibits NADPH oxidase–induced lipid peroxidation, reducing the arachidonic acid cascade. Dose: 10–15 mg/day. Mechanism:
o ↓ membrane peroxidation
o ↓ PLA₂ activation
o ↓ free AA release
o ↓ PGE₂ formation (independent of COX inhibition)
Key references:
• Prasad, Am J Clin Nutr, 2009
• Ho et al., Free Radic Biol Med, 2008
Selenium
• Required for GPx4, the enzyme that repairs lipid hydroperoxides directly in membranes.
• GPx4 is the only enzyme that can detoxify oxidized phospholipids inside the bilayer. Dose: 100 mcg 2–3×/week; more if inflammation is present. Note: Excess selenium causes fatigue and organ stress — more is not better.

3. Structural Lipid Support
Phosphatidylcholine (PC)
• The primary phospholipid of cell membranes.
• Essential for maintaining bilayer structure, fluidity, and repair.
• Supports ER–mitochondria lipid exchange, which is required for cardiolipin remodeling.
Stearic Acid
• A saturated fatty acid that “solidifies” and stabilizes membranes without promoting peroxidation.
• Helps maintain the optimal balance between membrane fluidity and rigidity. Sources: Cocoa butter, dark chocolate, beef tallow.

Why This Matters for Mitochondria
• PC stabilizes the outer mitochondrial membrane and supports lipid trafficking.
• PE (phosphatidylethanolamine) shapes the inner membrane and allows cardiolipin to organize respiratory complexes.
• Cardiolipin anchors the electron transport chain and is extremely sensitive to oxidation.
• GPx4, vitamin E, astaxanthin, zinc, and magnesium protect cardiolipin and PC from peroxidation and enzymatic degradation.
• Stearic acid and low-PUFA intake prevent fragile, oxidation-prone lipids from entering mitochondrial membranes.
Together, these nutrients maintain membrane integrity, mitochondrial efficiency, and resistance to oxidative stress.