Fatty Acid Synthesis and Regulation

  • Fatty Acid Synthesis Overview

    • 16-carbon saturated fatty acid synthetic pathway established.
    • Odd-chain fatty acids synthesized from propionic acid (3-carbon).
    • Majority of cell fatty acids exceed 18-26 carbons.

  • Extension of Fatty Acids

    • Longer fatty acids formed by adding 2-carbon units to carboxyl end using malonyl CoA.
    • Reactions similar to fatty acid synthase complex.
    • Enzymes for extension and desaturation located on cytoplasmic side of ER membrane.

  • Unsaturated Fatty Acids

    • Example: Conversion of stearate (18-carbon) to oleate (cis-∆9 double bond).
    • Desaturation occurs as CoA derivatives, not free fatty acids.
    • Mammals cannot introduce double bonds beyond carbon 9.
    • Essential dietary unsaturated fatty acids:
    • Linoleate (18:2 cis-∆9, ∆12) - ω-6
    • Linolenate (18:3 cis-∆9, ∆12, ∆15) - ω-3

  • Importance of Omega Fatty Acids

    • Precursors for other unsaturated fatty acids and hormones like arachidonate (4 double bonds) derived from linoleate.
    • Arachidonate synthesizes signaling molecules, eicosanoids.
    • Functions include inflammation, blood flow, and synaptic transmission.
    • Sources: canola oil, corn oil, nuts, fatty fish (e.g., salmon).

  • Clinical Insight: Aspirin's Mechanism

    • Aspirin modifies enzyme in prostaglandin synthesis, affecting inflammation and pain relief.
    • Inhibits enzyme converting arachidonic acid to PGH2, reducing downstream eicosanoids.

  • Regulation of Fatty Acid Synthesis

    • Acetyl CoA carboxylase regulates malonyl CoA synthesis, affecting fatty acid synthesis rates.
    • Influenced by energy levels (high glucose increases synthesis, low energy favors breakdown).

  • Hormonally Regulated Activity

    • Glucagon and epinephrine inhibit fatty acid synthesis during energy scarcity.
    • Insulin stimulates fatty acid synthesis via AMPK inhibition and enhancement of phosphatase 2A activity.

  • Citrate's Role

    • High levels indicate substrate availability for fatty acid synthesis, activating acetyl CoA carboxylase.
    • Citrate promotes dimer polymerization to active filaments.
    • Palmitoyl CoA induces depolymerization, indicating excess fatty acids.
    • Overall, these processes tightly regulate fatty acid metabolism in response to cellular energy states.