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1. Triglycerides (TAGs)

  • Definition: Molecules composed of glycerol and three fatty acids, forming the main form of fat storage in humans.

  • Characteristics:

    • Insoluble in water and require emulsification for absorption in the duodenum.

    • Composed of complex mixtures of individual triglycerides, with varied melting points.

    • High serum triglycerides are linked to atherosclerosis, increasing the risk of heart disease and stroke.

  • Metabolism:

    • TAGs are degraded to glycerol and free fatty acids (FFAs) for energy production.

    • Glycerol can enter gluconeogenesis or glycolysis in the liver.

    • FFAs are transported via albumin and oxidized in tissues to generate energy.

2. Fatty Acids (FAs)

  • Structure:

    • Long-chain carboxylic acids with hydrophobic hydrocarbon chains and a terminal hydrophilic carboxyl group.

    • Amphipathic nature, though the hydrophobic portion dominates in long-chain fatty acids.

  • Classification:

    • Saturated FAs: No double bonds; examples include palmitic and stearic acids.

    • Unsaturated FAs: One or more double bonds, classified as monounsaturated or polyunsaturated.

      • The addition of double bonds reduces melting points and caloric content.

  • Essential Fatty Acids:

    • Linoleic acid (omega-6) and linolenic acid (omega-3).

    • Necessary for prostaglandin synthesis and cellular functions; cannot be synthesized by mammals.

3. Synthesis and Degradation

  • Fatty Acid Synthesis:

    • Occurs in the cytoplasm, starting with acetyl-CoA and malonyl-CoA.

    • Requires NADPH and involves fatty acid synthase.

  • β-Oxidation:

    • A mitochondrial process where fatty acids are degraded in cycles, producing acetyl-CoA, NADH, and FADH₂.

    • Acetyl-CoA enters the citric acid cycle for further ATP production.

  • Unsaturated Fatty Acid Oxidation:

    • Requires additional enzymes, such as isomerase and reductase, for double-bond processing.

4. Triglyceride Synthesis and Storage

  • Glycerol Phosphate:

    • The precursor for TAG synthesis, produced from glucose via glycolysis in adipose tissue or glycerol via glycerol kinase in the liver.

  • Storage:

    • TAGs are stored in adipose tissue in anhydrous form for energy mobilization.

    • The liver exports TAGs as part of very low-density lipoproteins (VLDLs).

  • Fate of Glycerol:

    • Released glycerol is transported to the liver, phosphorylated to glycerol-3-phosphate, and enters metabolic pathways like gluconeogenesis.

5. Clinical Relevance

  • Dietary Considerations:

    • Excess saturated fatty acids and high triglycerides are linked to cardiovascular diseases.

    • Essential fatty acids are critical for growth, immune response, and inflammatory regulation.

  • Adipose Tissue Function:

    • Insulin regulates glucose uptake and glycerol phosphate production, affecting TAG synthesis.

    • In insulin deficiency, TAG synthesis is impaired, and lipolysis increases.