Lipid, Cholesterol, Total Cholesterol, Sphingolipid

  • Definitions
  1. Lipids
    1. Organic molecules containing Hydrocarbons
    2. Poorly soluble in water, but soluble in organic solvents
    3. Examples include free Fatty Acids, Triglycerides, phospholipids
  2. Cholesterol
    1. Lipid precursor for steroid Hormones, bile acids and Vitamin D
  3. Triglyceride
    1. Lipid composed of three molecules of Fatty Acid esterified to glycerol
    2. Triglycerides are a non-polar fat synthesized from Carbohydrates or ingested
    3. Triglycerides are High Energy Molecules that are stored for later use in animal adipose cells (fat cells)
  • Physiology
  • Lipid Functions
  1. fatMetabolism.png
  2. Energy Source
    1. Fatty Acids are stored for later energy use, bound to glycerol, as Triglycerides within fat cells
      1. Fatty Acids are synthesized by adding, in repeated cycles, 2 carbon atoms (acetyl CoA)
      2. Fatty Acid synthesis occurs in the cytoplasm of most cells to supply numerous uses including cell wall
    2. Fatty Acids are burned as fuel in the Kreb Cycle (TCA Cycle)
      1. Fatty Acids are degraded (oxidized) by removing, in repeated cycles, 2 carbon atoms (acetyl CoA)
      2. Energy from each extracted acetyl coA enters the Kreb Cycle
      3. Each Kreb Cycle generates NADH and FADH2 (total energy 17 ATP)
    3. Fats offer high energy stores (9 KCals/g) compared with Carbohydrates and proteins (4 kcals/g)
      1. Triglycerides are non-polar and bind less water (more compact than Carbohydrates, proteins)
      2. Each triglcyeride contains 3 Fatty Acids, each with 16 to 18 carbons (fueling 24-27 Kreb Cycles)
  3. Cell Membrane Components
    1. Cholesterol, glycolipids and phospholipids are important components of cell membranes
  4. Cholesterol Derivatives
    1. AdrenalFunction.png
    2. Cholesterol
      1. Cholesterol is a sterol ring structure (four interlinked aromatic rings) critical in physiology
      2. Cholesterol may either be ingested or synthesized
      3. Cholesterol synthesis (primarily in the liver)
        1. Acetyl CoA is converted to isoprene (5 carbon structure)
        2. Isoprene is combined with other isoprene molecules to form 10, 15 and 30 carbon rings
        3. Cholesterol (27 carbons) is among many Isoprenoids (isoprene derived molecules)
          1. Others Isoprenoids include all fat soluble Vitamins (A, D, E and K) and Coenzyme Q
    3. Steroid Hormones are derived from Cholesterol with unique side chains at the C17 carbon
      1. Pregnenolone (21 carbons) is derived from Cholesterol
        1. Sex Hormones, mineralcorticoids and Glucocorticoids are all formed from Pregnenolone
      2. Sex Hormones
        1. Testosterone (primarily synthesized in the Testes)
        2. Estrogen and Progesterone (primarily synthesized in the ovary)
        3. Dehydroepiandrosterone and Androstenedione (androgens synthesized in the Adrenal Cortex)
      3. Mineralcorticoids (e.g. Aldosterone, synthesized in the Adrenal Cortex)
      4. Glucocorticoids (e.g. Cortisol, synthesized in the Adrenal Cortex)
    4. Other Cholesterol derivatives and related Isoprenoids
      1. Bile Acids (derived from Cholesterol)
      2. Fat Soluble Vitamins (Vitamin A, Vitamin D, Vitamin E, Vitamin K)
      3. Coenzyme Q
  5. Fatty Acid Derivatives (esp. Arachidonic Acid Derivatives)
    1. General
      1. Basic structure is a 5 carbon ring "head" with two 6 to 9 carbon chain "legs"
      2. Functions vary by specific molecule, but function in general is summarized here
    2. Thromboxanes
      1. Increase Platelet aggregation
    3. Leukotrienes
      1. Leukocyte chemotaxis
    4. Prostacyclin
      1. Inhibits Platelet aggregation
      2. Vasodilates
    5. Prostaglandins
      1. Contracts Smooth Muscle (e.g. Vasoconstriction, bronchoconstriction, uterine contraction)
      2. Increases inflammatory response as well as pain and fever
  6. Sphingolipids
    1. Similar to Triglycerides with 2 exceptions
      1. Serine backbone (with a NH2 at the middle carbon) instead of a glycerol backbone
      2. First carbon group is a COOH instead of CH2-OH
    2. Sphingosine
      1. Analogous to a monoglyceride, with the first serine carbon attached to a Fatty Acid (palmitoyl CoA)
    3. Ceramide
      1. Analogous to a diglyceride, with the first 2 serine carbon chains attached to Fatty Acids
      2. Ceramide serves as a base for many molecules with different attachments at the third carbon
        1. Sphingomyelin (choline at the third carbon), a key component of the Myelin Sheath of nerves
        2. Cerebroside (Glucose or Galactose at the third carbon)
        3. Ganglioside (Oligosaccharide, multiple linked sugars and sialic acid, at the third carbon)
  7. Other important lipids
    1. Glycolipids
    2. Lipoproteins
  • Precautions
  1. Total Cholesterol <175 mg/dl in elderly: Increased mortality
    1. Schupf (2005) J Am Geriatr Soc 53:219-26 [PubMed]
  • Patient Education
  1. Mnemonic: Lower L-DL, Higher H-DL
  • References
  1. Goldberg (2001) Clinical Biochemistry, Medmasters, Miami, p. 17-23
  2. Guyton and Hall (2006) Medical Physiology, 7th Ed, Elsevier Saunders, Philadelphia, p. 829-58