Lipid Notes

Lipids

Lipid Overview

  • Lipids, often called fats (solid at room temperature), include oils (liquid at room temperature).
  • They are nonpolar, insoluble in water, and have diverse functions:
    • Energy storage
    • Structural components of membranes
    • Cell signaling

Lipid Classes

  • Free Fatty Acids: Essential fatty acids.
  • Triacylglycerols: Long-term energy storage.
  • Phospholipids: Primary membrane component.
  • Glycolipids: Membrane lipids.
  • Steroids: Including cholesterol and steroid hormones.

Fatty Acids

  • Derived from hydrocarbons, containing a carboxylic acid end.
  • Most have an even number of carbons (range: 4-36, common lengths: 12-24).
  • Saturation levels:
    • Saturated (0 double bonds)
    • Monounsaturated (1 double bond, MUFA)
    • Polyunsaturated (2+ double bonds, PUFA).
  • Energy: Lipids provide 99 kcal/g.

Fatty Acid Classification

  • Classified by:
    • Number of carbons (chain length)
    • Number of double bonds (saturation).
  • Chain Length:
    • Short chain: 4-6 carbons (e.g., Butyric acid)
    • Medium chain: 8-12 carbons (e.g., Lauric acid)
    • Long chain: 14-24 carbons (e.g., Palmitic acid, essential fatty acids).
  • Saturation:
    • Saturated: No double bonds (fats)
    • Monounsaturated: 1 double bond (oils)
    • Polyunsaturated: >1 double bond (oils).
  • Double bonds in PUFAs are methylene interrupted (CH2 in between), allowing flexible structure; adding double bonds creates kinks, preventing tight packing.

Fatty Acid Nomenclature

  • Two numbering systems:
    • Delta (Δ\Delta): Counts from the carboxyl end.
    • Omega (ω\omega): Counts from the methyl end.
  • Delta Nomenclature:
    1. Chain length
    2. Number of double bonds
    3. Positions of double bonds.
  • Omega Nomenclature:
    1. Chain length
    2. Number of double bonds
    3. Position of the first double bond.
  • Shortcut for conversions:
    • Delta to Omega: Subtract the LAST delta bond number from the total carbons.
    • Omega to Delta: Subtract the omega bond number from total carbons (gives the LAST delta bond); subtract 3 for each additional bond.
  • Common patterns: even number of carbons, 12-24 carbons, common bond between C9 & C10.

Common Fatty Acids

  • Short & Medium Chain Saturated Fatty Acids:
    • Butyric acid (4:0)
    • Caproic acid (6:0)
    • Caprylic acid (8:0)
    • Capric acid (10:0)
    • Lauric acid (12:0)
  • Long Chain Saturated Fatty Acids:
    • Myristic acid (14:0)
    • Palmitic acid (16:0)
    • Stearic acid (18:0)
    • Arachidic acid (20:0)
    • Lignoceric acid (24:0)
  • Monounsaturated Fatty Acids (MUFA):
    • Palmitoleic acid (16:1Δ\Delta9) / (16:1ω\omega7)
    • Oleic acid (18:1Δ\Delta9) / (18:1ω\omega9)
    • Nervonic acid (24:1Δ\Delta15) / (24:1ω\omega9)
  • Polyunsaturated Fatty Acids (PUFA):
    • Linoleic acid (18:2Δ\Delta9,12) / (18:2ω\omega6)
    • α\alpha-linolenic acid (ALA) (18:3Δ\Delta9,12,15) / (18:3ω\omega3)
    • Arachidonic acid (ARA) (20:4Δ\Delta5,8,11,14) / (20:4ω\omega6)
    • Eicosapentaenoic acid (EPA) (20:5Δ\Delta5,8,11,14,17) / (20:5ω\omega3)
    • Docosahexaenoic acid (DHA) (22:6Δ\Delta4,7,10,13,16,19) / (22:6ω\omega3)

Essential Fatty Acids

  • Humans cannot synthesize omega-3 and omega-6 fatty acids due to lack of desaturases.
  • Linoleic acid (18:2n-6) and alpha-linolenic acid (ALA; 18:3n-3) are most common essential fatty acids.
  • Omega-6 (Linoleic acid):
    • Functions: Prevent water loss, cell signaling, blood clotting.
  • Omega-3 (α\alpha-Linolenic acid):
    • Functions: Thins blood, anti-inflammatory, cell signaling, component of phospholipids in brain & retina.

Properties of Lipids

  • Longer carbon chain = less soluble in water.
  • More saturated = more solid; higher melting point.
  • Refined oils have higher smoke points.
  • MUFA & PUFA prone to rancidity due to oxidative breakage of double bonds.

Trans Fats

  • Formed via structural isomerization during hydrogenation.
  • Cis: same side; Trans: opposite side.
  • Trans fats behave like saturated fats in the body.
  • Health Impact: Increased risk of all-cause mortality and coronary heart disease.
  • FDA banned trans fats; removed 'generally recognized as safe' (GRAS) status.

Triacylglycerols (TG)

  • Also known as triglycerides.
  • Contain a glycerol backbone with 3 fatty acids attached.
  • Most are mixed and contain different fatty acids.
  • Function: Long-term energy storage.
  • Advantages over carbs: More reduced carbon atoms yield more energy; hydrophobic, so less water weight.
  • TG are stored in lipid droplets and adipocytes.
  • White adipocytes: energy storage (1 large lipid droplet)
  • Brown adipocytes: energy thermogenesis (many smaller lipid droplets)

Membrane Lipids

  • Amphipathic (hydrophilic & hydrophobic regions).
  • Classes: Phospholipids, Glycolipids, Sterols.

Phospholipids

  • Glycerophospholipids and Sphingophospholipids.
  • Glycerophospholipids: made from phosphatidic acid with a polar head group.
  • Functions: membrane component, stabilize membrane proteins, part of bile, lipid transport, storage of signaling molecules.
  • Glycerophospholipids with different polar head groups:
    • Phosphatidylcholine: Most common; in lung surfactant; prevents fatty liver
    • Phosphatidylethanolamine: Important for vesicles & mitochondrial membranes
    • Phosphatidylserine: Signaling; marker for apoptosis; clotting
    • Phosphatidylglycerol: In lung surfactant; precursor to cardiolipin
    • Phosphatidyl-inositol: Membrane anchoring & cell signaling
  • Cardiolipin: exclusively in the inner mitochondrial membrane.

Ether Phospholipids

  • Contain ether bond; e.g., Plasmalogen, Platelet activating factor.
    • Plasmalogen: Concentrated in nerve & muscle tissue.
    • Platelet activating factor: Released from white blood cells; stimulates platelet aggregation.

Sphingolipids

  • Sphingosine + Fatty acid = Ceramide
  • Important in cell signaling & regulation of cell death
  • Make up ~50% of lipids in stratum corneum
  • Sphingomyelin: In plasma membranes; concentrated in myelin sheath.

Glycolipids

  • Glycosphingolipids: Cerebrosides, Globosides, Gangliosides.
  • Often found on outer leaflet of plasma membrane; recognition sites.

Lipid Degradation

  • Occurs in the lysosome.
  • Phospholipid Degradation: Via phospholipases (A1, A2, C, D).
    • Phospholipase A2 releases arachidonic acid.
  • Sphingomyelin Degradation: Via sphingomyelinase.
  • Abnormal Accumulation of Glycolipids leads to diseases such as Tay-Sachs.

Sterols

  • Cholesterol: Steroid alcohol made in animal tissues, synthesized in the liver.
  • Precursor for steroid hormones, bile, Vitamin D.
  • Only found in animal products.
  • Plasma Membrane: Hydroxyl group of cholesterol faces the polar head group.
  • Steroid Hormones: Androgens, Estrogens, Progestagens, Corticosteroids.
  • Bile Acids: Cholic acid (cholate).
  • Vitamin D: Made from cholesterol in the skin.
  • Cholesterol ester: storage form.
  • Plant sterols compete with cholesterol for absorption.

Lipids as signals, cofactors & pigments.

  • Lipids functions:
    • Storage
      *Structure/membrane
      *Signaling.
Steroid Hormones
  • Bind to specific receptors in nucleus.
Intracellular Signals

  • Phosphatidylinositols are Intracellular Signal in protein kinase C pathway.

  • Sphingomyelin & Ceramide:
    *Potent regulators of protein kinases.
    *Ceramide production in muscles is associated with insulin resistance.

Eicosanoids
  • Paracrines– act on nearby cells, do not travel
  • Wide variety of functions from reproduction to inflammation to regulation of blood pressure.
  • Named as : PGH2 (Two letter abbreviation, Letter #3 is often listed in order of discovery ,Series number tells the # of double bonds it has).
Cyclooxygenase (COX) & Lipoxygenase (LOX):
  • ARA substrate for COX.
  • EPA substrate for LOX.
Eicosanoids in Inflammation
  • Mammals have 2 isoforms of cyclooxygenase
  • COX-1 regulate gastric secretions.
  • COX-2 mediate inflammation, pain & fever.
Anti inflammatory Lipids & proteins
  • Lipoxins, Resolvins & IL-10.
Balancing Omega-3 and Mercury Intakes

*Limit Fish consumption of: Shark, swordfish, tilefish & king mackerel to avoid mercury.
*FDA recommends 8-12 ounces of low-mercury fish per week.

Fat-Soluble Vitamins
  • Vitamins A, D, E, & K.
  • Vitamins A & D are Hormone Precursors
  • Vitamins E & K are Coenzymes for Redox Reactions.