LIPIDS AND LIPOPROTEINS IN CLINICAL CHEMISTRY

LIPIDS AND LIPOPROTEINS

  • Building Blocks: Fatty acids
  • Commonly referred to as fats
  • Soluble in organic solvents, insoluble in water
  • Made up of carbon and hydrogen (hydrocarbon molecules)
  • Good energy source (more on hydrocarbon chain structure)
FUNCTIONS:
  • Metabolic fuel: Provides 2x energy compared to carbohydrates or proteins
  • Cell membrane stability: Form lipid bilayers with hydrophilic and hydrophobic regions
  • Biochemical roles: Serve as precursors in metabolic pathways (e.g., steroid hormones)
MAJOR LIPIDS:
  • Phospholipids, Cholesterol, Triglycerides, Fatty acids, Fat-soluble vitamins (A, D, E, K)
    • Vitamin A – retinol
    • Vitamin D – calciferol (calcium bone growth)
    • Vitamin E – tocopherol (antioxidant)
    • Vitamin K – Phylloquinone (blood clotting factor)
CLASSIFICATION:
  1. Fatty acids
  2. Glycerol esters: Structures that contain glycerol
    • Triglycerides
    • Phosphoglycerides
  3. Sterol derivatives: Structures with rings
    • Cholesterol
    • Phytosterol
  4. Sphingosine Derivatives/Sphingolipids: Ceramide
  5. Terpenes: Include fat-soluble vitamins
FATTY ACIDS:
  • Long chains of carbon-hydrogen bonds terminating with a carboxyl group ($RCOOH$)
  • Building blocks of lipids; mostly bound to albumin (thus low serum concentration)
  • Hydrolysis of triglycerides creates free fatty acids
    • Examples: Palmitic acid, Stearic acid, Oleic acid, Linoleic acid, Arachidonic acid
CLASSIFICATIONS OF FATTY ACIDS:
  1. By Length:
    • Short-chain: 4-6 carbon atoms
    • Medium-chain: 8-12 carbon atoms
    • Long-chain: >12 carbon atoms
    • Very long-chain: >20 carbon atoms
  2. By Number of C=C Bonds:
    • Saturated: No double bonds (solid at room temperature)
    • Unsaturated: Contains double bonds (liquid at room temperature)
      • Monounsaturated: one double bond
      • Polyunsaturated: two or more double bonds
      • Double bonds can be in cis (same side) or trans (opposite side) configurations.
      • Elaidic acid is a major dietary fatty acid.
PHOSPHOLIPIDS:
  • Also known as phosphoglycerides; mostly derived from phosphatidic acid.
  • Composition: Glycerol, phosphate group, and two fatty acids.
  • Amphipathic: One part loves water (hydrophilic), while the other hates it (hydrophobic).
CLINICAL IMPORTANCE:
  • Triglycerides (TAG): Composed of 3 fatty acids and 1 glycerol; main form of stored energy.
    • Storage occurs in adipose tissues; hydrolysis releases fatty acids and energy.
  • Cholesterol: Synthesized primarily in the liver; vital for cell membranes and hormone production.
  • Lipoproteins: Complexes of lipids with proteins (apolipoproteins) essential for lipid transport in blood.
APOLIPOPROTEINS:
  • Functions:
    1. Maintain Solubility: Keep lipids in solution during circulation.
    2. Direct Lipids: Transport lipids to target organs.
    3. Structural Integrity: Maintain the lipoprotein complex's structure.
    4. Receptor Ligands: Serve as recognition signals.
    5. Enzyme Modulation: Act as activators or inhibitors of enzymes modifying lipoproteins.
COMMON APOLIPOPROTEINS:
  • Apo A1: Activates LCAT, involved in HDL synthesis.
  • Apo B:
    • B-100: Major in VLDL and LDL
    • B-48: Specific to Chylomicrons
  • Apo C: Involved in lipoprotein lipase activity.
LIPID METABOLISM:
  1. Exogenous Pathway: Involves the formation of chylomicrons from dietary lipids, facilitating transport via the bloodstream.
  2. Endogenous Pathway: Formation and utilization of VLDL from liver sources, transporting TAG to tissues.
  3. Reverse Cholesterol Transport: HDL’s role in returning excess cholesterol to the liver.
DISORDERS RELATED TO LIPIDS AND LIPOPROTEINS:
  • Dyslipidemias: Affected lipid profiles leading to conditions like atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PVD), and cerebrovascular disease (CVD).
  • Hyperlipoproteinemia: Includes familial and acquired forms that increase specificity of TAG and cholesterol levels due to various genetic and environmental factors.
GUIDELINES FOR LABORATORY ASSESSMENT:
  • Desirable Ranges:
    • TAG < 150 mg/dL
    • Total Cholesterol < 200 mg/dL
    • LDL-C < 130 mg/dL
    • HDL-C > 55 mg/dL (higher is better)
THERAPIES FOR DYSLIPIDEMIAS:
  • Statins: Inhibit cholesterol synthesis.
  • Bile Acid Sequestrants: Facilitate fat emulsification.
  • Niacin: Increases HDL levels.
  • Ezetimibe: Reduces cholesterol absorption from the gut.