Essential Fatty Acids and Lipids

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Lipid Basics - Fatty Foundations

  • Lipids: Organic compounds, insoluble in water, soluble in organic solvents.
    • Functions: Energy storage, structural components (membranes), signaling molecules, insulation.
  • Fatty Acids (FAs): Hydrocarbon chains with a carboxyl group (-COOH).
    • Saturated (SFAs): No double bonds (e.g., Palmitic, Stearic).
    • Unsaturated: One or more double bonds.
      • Monounsaturated (MUFAs): One double bond (e.g., Oleic acid).
      • Polyunsaturated (PUFAs): ≥2 double bonds (e.g., Linoleic, Linolenic).
  • Triglycerides (TGs): Glycerol + 3 FAs; main storage form of fat.
  • Phospholipids: Glycerol + 2 FAs + phosphate group; key for cell membranes.

Triglyceride and Phospholipid Structure

⭐ Most naturally occurring unsaturated fatty acids have cis-configuration double bonds, causing a kink in the chain, which increases membrane fluidity.

  • Amphipathic lipids: Possess both hydrophilic and hydrophobic regions (e.g., phospholipids).

Essential Fatty Acids - The Must-Haves

  • EFAs: Polyunsaturated fatty acids (PUFAs) not synthesized de novo by humans; vital dietary components.
  • Two Main Families:
    • Linoleic Acid (LA): Omega-6 (ω-6). $C_{18}H_{32}O_2$ (18:2, n-6). Precursor to Arachidonic Acid (AA).
      • Sources: Safflower, sunflower, corn, soybean, cottonseed oils.
    • Alpha-Linolenic Acid (ALA): Omega-3 (ω-3). $C_{18}H_{30}O_2$ (18:3, n-3). Precursor to EPA & DHA.
      • Sources: Flaxseed, chia seeds, walnuts, canola oil, soy oil.
  • Key Functions:
    • Maintain cell membrane structure & fluidity.
    • Synthesis of eicosanoids (prostaglandins, thromboxanes, leukotrienes).
    • Nerve transmission, vision development.
    • Skin barrier integrity; prevent water loss.
  • Deficiency Symptoms:
    • Scaly dermatitis (phrynoderma), eczema.
    • Poor wound healing, increased infections.
    • Growth retardation (especially in infants).
    • Alopecia, thrombocytopenia.
  • 📌 Mnemonic: "Linoleic (ω-6) & Alpha-Linolenic (ω-3) Are Absolutely Necessary." (LALA AN) Essential Fatty Acids Metabolic Pathways

⭐ Deficiency of EFAs can manifest as phrynoderma ("toad skin"), particularly seen with linoleic acid deficiency.

EFA Metabolism - Pathway Power-Up

  • Core Process: EFAs (Linoleic ω-6, α-Linolenic ω-3) undergo sequential desaturation (Δ6, Δ5 desaturases) & elongation.
  • Δ6 Desaturase: Rate-limiting, shared by ω-6/ω-3 pathways; inhibited by trans fats, alcohol.
  • Key Products & Actions:
    • ω-6 (via Arachidonic Acid - AA):
      • COX pathway: Prostaglandins (PG₂), Thromboxanes (TXA₂) → Pro-inflammatory, pro-aggregatory.
      • LOX pathway: Leukotrienes (LTB₄, LTC₄/D₄/E₄) → Inflammation, bronchoconstriction.
    • ω-3 (via Eicosapentaenoic Acid - EPA):
      • COX pathway: PG₃, TXA₃ → Less inflammatory, anti-aggregatory.
      • LOX pathway: LT₅ → Less potent inflammatory effects.
    • DHA (from EPA): Vital for brain & retinal development.
    • DGLA (ω-6 intermediate): Forms anti-inflammatory PGE₁ via COX.
  • Maintain healthy ω-6:ω-3 ratio (e.g., ~4:1).
  • ⭐ > Aspirin causes irreversible acetylation and inhibition of COX-1 and COX-2 enzymes, blocking eicosanoid synthesis.

Clinical Significance - Health Impacts

  • Cardiovascular Health: Omega-3s (EPA, DHA) ↓ triglycerides, ↓ blood pressure, ↓ arrhythmia risk. Omega-6s (Linoleic Acid) can be pro-inflammatory if ω-6/ω-3 ratio is high.
  • Neural Development: DHA is crucial for brain and retina development in infants.
  • Inflammation: EPA is a precursor to anti-inflammatory eicosanoids. Arachidonic acid (ω-6) can produce pro-inflammatory eicosanoids.
  • Skin Health: EFAs maintain skin barrier function; deficiency leads to dermatitis.
  • Trans Fats: ↑ LDL, ↓ HDL, ↑ risk of coronary heart disease.

Omega-6 and Omega-3 Metabolic Pathways and Inflammation

⭐ Deficiency of Essential Fatty Acids (EFAs) can manifest as scaly dermatitis, alopecia, thrombocytopenia, and poor wound healing. Linoleic acid deficiency is particularly associated with scaly skin lesions (phrynoderma or toad skin).

High‑Yield Points - ⚡ Biggest Takeaways

  • Linoleic acid (ω-6) and α-linolenic acid (ω-3) are the primary Essential Fatty Acids (EFAs).
  • EFA deficiency manifests as dermatitis, hair loss, and poor wound healing.
  • Arachidonic acid (derived from linoleic acid) is key for eicosanoid synthesis (e.g., prostaglandins, leukotrienes).
  • DHA and EPA (derived from α-linolenic acid) are vital for neural and retinal development.
  • Omega-3 FAs generally exhibit anti-inflammatory effects, while many Omega-6 FAs derivatives are pro-inflammatory.
  • Trans fats adversely impact lipid profiles (elevate LDL, decrease HDL), increasing cardiovascular disease risk.

Practice Questions: Essential Fatty Acids and Lipids

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A patient with high triglycerides (TG) esterified with long-chain fatty acids (LCFA) presents with fatigue, and a biopsy of the muscle shows fat vacuoles. What is the most likely diagnosis?

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Flashcards: Essential Fatty Acids and Lipids

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Breast milk is rich in _____saturated fat, which is necessary for myelination

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Breast milk is rich in _____saturated fat, which is necessary for myelination

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