Essential Fatty Acids (EFAs) & Eicosanoid Precursors
| Linoleic Acid (LA): | 18:2 (ω-6) → Precursor to Arachidonic Acid |
| α-Linolenic Acid (ALA): | 18:3 (ω-3) → Precursor to EPA and DHA |
| Human Desaturase Limit: | Carbon-9 (Δ9 desaturase) (Cannot insert bonds past C9) |
| Clinical Deficit Signature: | Scaly Dermatitis & Poor Wound Healing |
High-Yield Core Realities:
- The Desaturase Barrier: Human hepatocytes possess Δ4, Δ5, Δ6, and Δ9 desaturases, allowing them to easily place double bonds near the carboxyl end of a fatty acid. However, mammals completely lack the enzymatic machinery to introduce double bonds past the carbon-9 position from the carboxyl end. Because linoleic acid (double bonds at C9, C12) and α-linolenic acid (bonds at C9, C12, C15) contain variations beyond this boundary, they must be obtained entirely from dietary sources.
- The ω-6 Downstream Cascade: Linoleic acid undergoes sequential elongation and desaturation via Δ6-desaturase to yield Arachidonic Acid (20:4, ω-6). Arachidonic acid integrates directly into the phospholipid bilayer. Upon activation by Phospholipase A2, it enters the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, generating primarily pro-inflammatory series-2 prostanoids (PGE2, TXA2) and series-4 leukotrienes (LTB4).
- The ω-3 Cardioprotective Shunt: α-Linolenic acid serves as the starting building block for Eicosapentaenoic acid (EPA, 20:5) and Docosahexaenoic acid (DHA, 22:6). EPA is metabolized into series-3 prostanoids (PGE3, TXA3) and series-5 leukotrienes. TXA3 is a vastly weaker platelet aggregator compared to arachidonic-derived TXA2, which explains why diets rich in fish oil shift the overall physiological balance away from thrombosis and systemic inflammation.
- The Triene-to-Tetraene Diagnostic Ratio: When a patient suffers from severe, prolonged fat malabsorption or receives long-term Total Parenteral Nutrition (TPN) lacking lipids, the body attempts to compensate for EFA depletion. The liver shifts to elongating oleic acid (18:1, ω-9), producing Mead Acid (20:3, ω-9). A serum triene (Mead acid) to tetraene (arachidonic acid) ratio greater than 0.2 serves as the definitive laboratory diagnostic standard for essential fatty acid deficiency.