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.