BA

Lipid Biochemistry Notes

Lipids

  • Lipids - Palmer College of Chiropractic Palmer PASS. Creator : Seth Christensen

Bonds & Structure

  • Lipids are structured with a hydrocarbon chain and a carboxylic acid group.
  • They can be represented as R-COOH, where R is the hydrocarbon chain.
  • The carboxylate form is R-COO^{-}.
  • Fatty acids can be saturated or unsaturated, depending on the presence of double bonds.
  • Saturated fatty acids have no double bonds.
  • Unsaturated fatty acids have one or more double bonds.
  • Monounsaturated fatty acids have one double bond.
  • Polyunsaturated fatty acids have multiple double bonds.

Lipid Nomenclature

  • Nomenclature involves counting carbons and identifying the location of double bonds.
    • Example: 20:4(5,8,11,14) indicates a 20-carbon chain with double bonds at positions 5, 8, 11, and 14.
    • Omega notation (w) counts from the methyl end to identify the position of the first double bond.
    • Example: 20:4w6 indicates a 20-carbon chain with the first double bond at position 6 from the omega end.
  • Examples of fatty acids and their omega designations:
    • Arachidonic acid: 20:4w6

Lipid Nomenclature Continued

  • 20:5w3 indicates a 20-carbon chain with 5 double bonds, starting from the third carbon from the omega end.

Fatty Acids: SFA, MUFA, PUFA

  • SFA (Saturated Fatty Acids) have the form X:0, where X is the number of carbons.
  • MUFA (Monounsaturated Fatty Acids) have the form X:1w?.
  • PUFA (Polyunsaturated Fatty Acids) have the form X:?w?.
  • Examples of saturated fatty acids:
    • Propionic acid: 3 carbons.
    • Butyric acid: 4 carbons (found in butter).
    • Caproic acid: 6 carbons.
    • Caprylic acid: 8 carbons.
    • Capric acid: 10 carbons.
    • Lauric acid: 12 carbons.
    • Myristic acid: 14 carbons.
    • Palmitic acid: 16 carbons (produced in the liver).
    • Stearic acid: 18 carbons.
  • Examples of unsaturated fatty acids:
    • Palmitoleic acid: 16:1w7.
    • Oleic acid: 18:1w9.
    • Alpha-linolenic acid (ALA): 18:3w3.
    • Arachidonic acid (ARA): 20:4w6.
    • Eicosapentaenoic acid (EPA): 20:5w3.
    • Docosahexaenoic acid (DHA): 22:6w3.
    • Lignoceric acid: 24:0.
    • Nervonic acid: 24:1w9.

Lipid Types

  • Isoprenoids: Includes compounds like cholesterol, ergosterol, and Vitamin D.
  • Glycerolipids: Includes triacylglycerols and phospholipids.
  • Phospholipids: Important for cell membranes.
  • Sphingolipids: Includes sphingomyelin, cerebrosides, gangliosides.
  • Steroids: Includes cholesterol, steroid hormones.
  • Eicosanoids: Signalling molecules, derived from fatty acids.

Triacylglycerols (TG)

  • Formed by combining glycerol (an alcohol) with fatty acids via dehydration/condensation.
  • Breaking TG occurs through hydrolysis by adding water.
  • Typically, saturated fatty acids (SFA) are found at the sn-1 position.
  • Unsaturated fatty acids (UFA) are usually at the sn-2 position.
  • The sn-3 position can have either SFA or UFA.
  • Reaction: Alcohol + Fatty acid -> Triacylglycerol

Phospholipids and Sphingolipids

  • Phospholipids have a hydrophilic (polar) head and a hydrophobic (nonpolar) tail.
    • The hydrophilic head contains a phosphate group and can include sugars, as found in glycocalyx.
    • The hydrophobic tail consists of fatty acids and ceramide.
  • Sphingolipids also have a polar head and nonpolar tail
  • Glycerophospholipids are common phospholipids.
  • Glycosphingolipids are sphingolipids with sugar moieties.
  • Examples of glycerophospholipids include phosphatidylcholine (lecithin).
  • Sphingomyelin is a type of sphingophospholipid.
  • Gangliosides are glycosphingolipids containing more than two sugars, especially abundant in the brain (150%).
  • Phospholipids and their functions:
    • Membrane anchoring.
    • Apoptosis (cell signaling).
    • Lung surfactant.
    • Involved in protein kinase pathways.
    • Bone formation.
    • Cardiolipin.

Vitamin D

  • Vitamin D exists in two forms: D2 (ergocalciferol) found in plants and D3 (cholecalciferol) found in animals.

  • 7-dehydrocholesterol in the skin is converted to cholecalciferol upon exposure to sunlight.

  • Vitamin D acts as a prohormone.

  • Cholecalciferol is inactive and requires activation.

  • Vitamin D's mechanism involves binding to a receptor in the nucleus, leading to protein synthesis.

  • The liver converts cholecalciferol to 25-hydroxycholecalciferol (calcidiol) via 25-hydroxylase.

  • 25-hydroxyvitamin D is a biomarker for vitamin D status.

  • Kidneys convert calcidiol to 1,25-dihydroxycholecalciferol (calcitriol).

  • Calcidiol to calcitriol conversion is activated by parathyroid hormone (PTH).

  • Vitamin D deficiency can cause rickets in children and osteomalacia in adults.

    • Deficient: < 20 ng/mL

  • Calcitriol is concentrated in the kidneys and regulates calcium/phosphorus homeostasis and bone mineralization.

  • 24-hydroxylase detoxifies calcitriol, forming 1,24,25-trihydroxyvitamin D.

  • Vitamin D requires iron for its function.

Fat as Signalling Compounds

  • Fatty acids serve as precursors for signaling compounds.

    *Cox (Cyclooxygenase) products from arachidonic acid (20:4w6): Prostaglandins and Thromboxanes involved in inflammation formation clot and pain, anaphylactic shock fever etc.

    *Lox (Lipoxygenase) product : Lipoxins: involved in reasoning and resolution

  • Examples of cyclooxygenase (COX) products derived from fatty acids:

    • Prostaglandins (PG).
    • Thromboxanes (TX).

  • Examples of lipoxygenase (LOX) products derived from fatty acids:

    • Lipoxins (LX).
    • Leukotrienes (LT).

  • EPA and DHA give rise to resolvins, protectins, and maresins, which are anti-inflammatory.

Lipid Digestion

  • Lipids are emulsified in the mouth and stomach with the help of lingual lipase and gastric lipase.
  • In the mouth, lingual lipase is active, especially in babies.
  • In the stomach, gastric lipase digests triacylglycerols (TGs).
  • Peristalsis and retropulsion occur in the stomach.
  • In the small intestine (duodenum, jejunum, ileum), pancreatic enzymes and bile aid in digestion.
  • Pancreatic enzymes include:
    • Pancreatic lipase: breaks down triacylglycerols.
    • Phospholipase A2: removes fatty acids from phospholipids.
    • Cholesterol esterase: removes fatty acids from cholesterol esters.
  • Bile emulsifies fats and is secreted from the gallbladder.
  • Fermentation by gut bacteria occurs in the cecum and colon, producing short-chain fatty acids.

Lipid Absorption

  • Lipid absorption occurs in the small intestine (duodenum and jejunum).
  • Short-chain fatty acids (SCFA) and medium-chain fatty acids (MCFA) are absorbed directly into the portal vein and carried by albumin.
  • Long-chain fatty acids (LCFA) are emulsified into micelles with bile salts.
  • Micelles transport lipids to the enterocytes for absorption.
  • Inside enterocytes, lipids are re-esterified and packaged into chylomicrons.
  • Chylomicrons are a form of active transport that are released into the lymphatic system.
  • Fat-soluble vitamins (A, D, E, K) are absorbed along with lipids.
  • Lysophospholipids are formed outside the enterocytes by phospholipases.

Lipid Metabolism

  • Lipid Metabolism: De novo (L) of new fatty acid synthesis from the beginning.
  • Liver - m. c. made = plamitate
  • Carbs -> fatty acid -> TG FA synthesis
  • VLDL-TG: Both exogenous and endogenous
  • LPL (lipoprotein lipase) function is to break down TG -> 3 FA + glycerol which allows lipids inside cells.
  • (expressed on extracellular membrane)
  • (activated by apoproteins on chylomicrons & VLPL
  • Stimulate: apoC-II
  • Inhibits: apoC-III
  • Chylomicrons -> TG with FA uptake in muscle, adipocytes
  • LOL -> Receptor mediated endocytosis digested by Tysosome Cholersterol with bound cholesterol ester for storage. LDL receptors can not have LOL picked up in HDL, free cholesterol is in HDL
  • Enzyme: LCAT (lecithin cholesterol acyl) transferase which esterifies during process. It is Copper/Cu dependent.