Essential Architecture
In a previous essay, I described polyunsaturated fatty acids as respiratory inhibitors—compounds that damage cardiolipin, poison cytochrome c oxidase, and can induce a torpor-like metabolic state. This essay goes deeper into that story, exploring a distinction that determines when those mechanisms activate and when they don’t.
Building materials and fuel are not the same thing.
You don’t burn lumber to heat your house while your walls are falling down. You don’t metabolize muscle protein for energy while trying to get stronger. And you shouldn’t be oxidizing polyunsaturated fatty acids in your mitochondria when those same fatty acids are essential structural components of every membrane in your body.
PUFAs aren’t simply “toxic” or “healthy”—they’re building blocks that cause problems when they end up in the wrong metabolic context. This essay is about that distinction: why it matters, what drives the shift from structure to fuel, and how it fits into the framework I’ve been developing.
The Two Categories
Macronutrients serve two fundamentally different purposes: they provide structure, or they provide energy. Getting this wrong—treating a structural molecule as fuel, or expecting a fuel molecule to build anything—is a category error with metabolic consequences.
| Category | Purpose | Examples |
|---|---|---|
| Structural | Building blocks for tissues, membranes, signaling molecules | Essential amino acids, essential fatty acids |
| Energetic | Fuel for ATP production | Glucose, saturated fats |
What PUFAs Actually Do
The textbook role of polyunsaturated fatty acids is structural. When incorporated into phospholipids, they determine membrane properties: - Fluidity: PUFA-containing membranes are more fluid - Thickness: DHA-rich phospholipid membranes are thinner - Flexibility: PUFAs confer mechanical resilience
In the brain, DHA constitutes 20-30% of brain lipids and is highly enriched in neuronal and synaptic membranes, where it is incorporated preferentially into phosphatidylethanolamine and phosphatidylserine.
PUFAs Are Not Preferred Fuel
Polyunsaturated fatty acids with three or more double bonds are usually not utilized as a source of energy. Most PUFAs exist in phospholipids, constructing cell membranes and serving as substrates for enzymes that produce signaling molecules.
Research shows that mitochondria deliberately maintain higher PUFA content in their phospholipids than the cell as a whole. Dietary n-3 PUFA, particularly DHA, has profound effects on mitochondrial membrane phospholipid composition, increasing cardiolipin content—a tetra-acyl phospholipid unique to mitochondria and essential for optimal function. The mitochondria are hoarding PUFAs for structural purposes, not burning them. Long-chain PUFAs like DHA appear to be preferentially oxidized in peroxisomes rather than mitochondria.
The Lands Cycle: Continuous Remodeling
Membranes aren’t static. They’re constantly being remodeled through the Lands cycle. This is membrane maintenance—how the cell repairs oxidized lipids, adjusts fluidity, and incorporates essential fatty acids.
When Building Blocks Become Fuel
Under certain conditions, PUFAs that should be structural components end up being oxidized as fuel. When this happens: 1. Structural needs go unmet. Membrane architecture degrades. 2. The oxidation itself is problematic. PUFA oxidation produces peroxidation products like 4-hydroxynonenal (4-HNE) that inhibit cytochrome c oxidase and damage cardiolipin.
Cardiolipin, localized almost exclusively within the inner mitochondrial membrane, is particularly rich in unsaturated fatty acids. Because cardiolipin plays a pivotal role in facilitating the activities of electron transport complexes, changes that increase its susceptibility to oxidative damage are deleterious to normal mitochondrial function.
The problem isn’t that you ate PUFAs. The problem is that PUFAs ended up being burned instead of being built with.
What Drives PUFAs Into the Wrong Stream?
- Inadequate dietary EFA intake
- Chronic stress and excessive PLA2 activation
- Catabolism exceeding anabolism
- Excess PUFA relative to structural capacity
Integrating With the Framework
Form maintenance requires adequate structural substrates. You can’t maintain cellular architecture without the building blocks—protein for muscle and enzymes, EFAs for membranes.
Velocity requires appropriate fuel. T3 increases metabolic rate, which increases demand for ATP. Glucose and saturated fats are the efficient fuels.
The failure mode is mismatch. When structural substrates are inadequate, the body cannibalizes existing structures.
The practical implication: adequate EFA intake is protective, not harmful. If you’re providing the building blocks, the Lands cycle can maintain membrane architecture.